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Waste Disposal Information
All toxic materials were disposed of in accordance with "Prudent Practices for Disposal of Chemicals from Laboratories"; National Academy Press; Washington, DC, 1983.
Vinylglycine is a natural amino acid found in mushrooms.3 It is an inhibitor of pyridoxal-linked aspartate aminotransferase,4 and has also been postulated as an intermediate in the enzymatic conversion of homoserine to threonine5 and a-ketobutyrate.6 Protected vinylglycine is also a versatile asymmetric starting material for synthesis.7 Variants have been prepared in racemic,8-13 optically active,14 optically pure,215-17 and isotopically labeled form.413'18-20 This procedure is derived from our earlier publication2 and contains improvements in procedure and scale-up.
1. Department of Chemistry, University of California, Berkeley, CA 94720.
2. Afzali-Ardakani, A.; Rapoport, H. J. Org. Chem. 1980, 45, 4817.
3. Dardenne, G.; Casimir, J.; Marlier, M.; Larsen, P. O. Phytochemistry 1974, 13, 1897.
4. (a) Rando, R. R.; Relyea, N.; Cheng, L. J. Biol. Chem. 1976, 251, 3306; (b) Rando, R. R. Biochemistry 1974, 13, 3859.
5. Flavin, M.; Slaughter, C. J. Biol. Chem. 1960, 235,1112.
6. Posner, B. I.; Flavin, M. J. Biol. Chem. 1972, 247, 6402.
7. Shaw, K. J.; Luly, J. R.; Rapoport, H. J. Org. Chem. 1985, 50, 4515.
8. Friis, P.; Helboe, P.; Larsen, P. O. Acta Chem. Scand., Ser. B 1974, 28, 317.
9. Baldwin, J. E.; Haber, S. B.; Hoskins, C.; Kruse, L. I. J. Org. Chem. 1977, 42, 1239.
10. Hudrlik, P. F.; Kulkarni, A. K. J. Am. Chem. Soc. 1981, 103, 6251.
11. Vyas, D. M.; Chiang, Y.; Doyle, T. W. J. Org. Chem. 1984, 49, 2037.
12. Greenlee, W. J. J. Org. Chem. 1984, 49, 2632.
13. Fitzner, J. N.; Pratt, D. V.; Hopkins, P. B. Tetrahedron Lett. 1985, 26, 1959.
14. Schöllkopf, U.; Nozulak, J.; Groth, U. Tetrahedron 1984, 40, 1409.
15. Hanessian, S.; Sahoo, S. P. Tetrahedron Lett. 1984, 25, 1425.
16. Barton, D. H. R.; Crich, D.; Hervé, Y.; Potier, P.; Thierry, J. Tetrahedron 1985, 41, 4347.
17. Pellicciari, R.; Natalini, B.; Marinozzi, M. Synth. Commun. 1988, 18, 1715.
18. Chang, M. N. T.; Walsh, C. T. J. Am. Chem. Soc. 1981, 103, 4921.
19. Sawada, S.; Nakayama, T.; Esaki, N.; Tanaka, H.; Soda, K.; Hill, R. K. J. Org. Chem. 1986, 51, 3384.
30. Rosegay, A.; Taub, D. Synth. Commun. 1989, 19, 1137.
Chemical Abstracts Nomenclature (Collective Index Number); (Registry Number)
N-(Benzyloxycarbonyl)-L-vinylglycine methyl ester: 3-Butenoic acid, 2-[[(phenylmethoxy)carbonyl]amino]-, methyl ester, (S)- (10); (75266-40-9) N-(Benzyloxycarbonyl)-L-methionine methyl ester: L-Methionine, N-[(phenylmethoxy)carbonyl]-, methyl ester (9): (56762-93-7)
L-Methionine methyl ester hydrochloride: Methionine, methyl ester, hydrochloride, L- (8); L-Methionine, methyl ester, hydrochloride (9); (2491-18-1)
Benzyl chloroformate: Formic acid, chloro-, benzyl ester (8); Carbonochloride acid, phenylmethyl ester (9); (501-53-1)
Glycine (8,9); (56-40-6)
Methyl L-2-(benzyloxycarbonylamino)-4-(methylsulfinyl)butanoate: Butanoic acid,
4-(methylsulfinyl)-2-[[(phenylmethoxy)carbonylJamino]-, methyl ester,
(S)- (10); (75266-39-3)
L-Vinylglycine hydrochloride: 3-Butenoic acid, 2-amino-, hydrochloride, (S)- (10); (75266-38-5)
L-Methionine (8,9); (63-68-3)
(R)-(-)-10-METHYL-1(9)-OCTAL-2-ONE (2(3H)-Naphthalenone, 4,4a,5,6,7,8-hexahydro-4a-methyl-, (R)-)
Bubmitted by G. Revial and M. Pfau.1
Checked by Graham N. Maw and Robert K. Boeckman, Jr.
A. /mines (1). In a 1000-mL, round-bottomed flask, fitted with a toluene-filled Oean-Stark water separator, 100.0 g (0.825 mol) of (S)-(-)-a-methylbenzylamine (Note 1), 92.5 g (0.825 mol) of 2-methylcyclohexanone (Note 2) and 100 mL of toluene
are heated at reflux temperature under a nitrogen atmosphere. After 24 hr, ca. 15 mL of water (ca. 100% theor.) has been removed azeotropically.
B. (R)-(+)-2-Methyl-2-(3-oxobutyl)cyclohexanone (2). The solution of imines 1 is cooled in an ice bath and 72.5 mL (61.0 g, 0.870 mol, ca. 1.05 equiv) of freshly distilled methyl vinyl ketone (Note 3) is added with a syringe, with magnetic stirring, under a nitrogen atmosphere. The flask is then heated at ca. 40°C for 24 hr.
The slightly yellow solution is cooled in an ice bath and 60 mL of glacial acetic acid (ca. 1 mol) and 50 mL of water are added. Hydrolysis is achieved by stirring the heterogeneous mixture at room temperature for 2 hr. The now clear solution is poured into a 2000-mL separatory funnel containing 100 mL of brine and 160 mL of water and is extracted five times with a 50:50 mixture of ether-petroleum ether (35-60cC) (1000-mL total amount). The organic phase is washed efficiently with 20 mL of 10% hydrochloric acid, 20 mL of water, and two 10-mL portions of brine.
The aqueous layer is kept for recovery of the amine (see D below).
The pale yellow organic layer is dried over a small amount of anhydrous magnesium sulfate and filtered. The solvents are removed with a rotary evaporator at ca. 40°C and the crude diketone 2 (ca. 145 g) is used directly for the next step.