Acetic Anhydride → HCID 86744053, compound

HRID 2108278Notes

Reaction equation

HRID 2108278 reaction equation
[SH:1][CH:2]([CH:14]([C:19]([NH:21][C@H:22]([C:32]([NH:34][CH3:35])=[O:33])[CH2:23][C:24]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=1)=[O:20])[CH2:15][CH:16]([CH3:18])[CH3:17])[CH2:3][C:4]([O:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:5].[C:36](OC(=O)C)(=[O:38])[CH3:37].CN1CCOCC1>C(Cl)(Cl)Cl>[C:36]([S:1][CH:2]([CH:14]([C:19]([NH:21][C@H:22]([C:32]([NH:34][CH3:35])=[O:33])[CH2:23][C:24]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=1)=[O:20])[CH2:15][CH:16]([CH3:17])[CH3:18])[CH2:3][C:4]([O:6][CH2:7][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)=[O:5])(=[O:38])[CH3:37]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 79724-MethylmorpholineHCID 44352499HCID 44352499, compound

Product 1

HCID 86744053HCID 86744053, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
0 °C

Procedure

The benzyl ester (D8) (41 g, 0.088 mole) was dissolved in thiolacetic acid (170 ml) and left to stand at room temperature under nitrogen for 19 days. Volatile material was removed in vacuo and the residue chromatographed on silica gel with initially ether, rising slowly to ethyl acetate. After removal of high Rf impurities the title compound was obtained as a mixture of diastereomers as a pale yellow foam (29.76 g, 62.4%). (Found: C, 64.29; H, 7.16; N, 4.86. C29H38N2SO6 requires C, 64.18; H, 7.06; N, 5.16%). Later fractions contained olefinic material (D8). However, more complete reaction can be obtained by addition of a suitable base, for example triethylamine. An aliquot (2 ml) was removed from the above reaction mixture after 14 days, treated with triethylamine (3 drops) and left to stand for a further 5 days at room temperature under nitrogen. The same work-up procedure as for the bulk of the reaction mixture described above gave only the diastereomer mixture (E3) with no olefinic material remaining. 3-Mercapto-6-methyl-4-[[[1-(S)-[(methylamino)carbonyl]2-(4-methoxyphenyl)ethyl]amino]carbonyl]heptanoic acid, benzyl ester (E4, Isomer A, 2.0 g 0.004 mol) was dissolved in chloroform (100 ml) under an atmosphere of nitrogen. The reaction mixture was cooled to 0° C. and acetic anhydride (2.04 g, 0.02 mol) was added followed by N-methylmorpholine (2.02 g, 0.02 mol). The reaction mixture was allowed to warm to room temperature, then stirred under nitrogen for 3 days.

Workup

  1. temperatureto warm to room temperature

Sources & evidence

ORD record
ord-228c721730e549efa6a642b844a4276b
Source dataset
uspto-grants-1990_06
Patent number
US04937243

Reaction notes

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