Ethanol → tert-butyl 3(R)-[1-ethoxycarbonyl-3-(p-tolyl)propyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetate

HRID 1284940Notes

Reaction equation

HRID 1284940 reaction equation
C(O)C.[NH2:4][C@@H:5]1[C:11](=[O:12])[N:10]([CH2:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C:9]2[CH:21]=[CH:22][CH:23]=[CH:24][C:8]=2[S:7][CH2:6]1.[CH3:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32][CH2:33][C:34](=O)[C:35]([O:37][CH2:38][CH3:39])=[O:36])=[CH:28][CH:27]=1>[C].[Pd].C(O)(=O)C>[CH2:38]([O:37][C:35]([CH:34]([NH:4][C@@H:5]1[C:11](=[O:12])[N:10]([CH2:13][C:14]([O:16][C:17]([CH3:19])([CH3:20])[CH3:18])=[O:15])[C:9]2[CH:21]=[CH:22][CH:23]=[CH:24][C:8]=2[S:7][CH2:6]1)[CH2:33][CH2:32][C:29]1[CH:28]=[CH:27][C:26]([CH3:25])=[CH:31][CH:30]=1)=[O:36])[CH3:39]

Participants

6

Reactant 3

HCID 702EthanolHCID 13201329Ethyl 4-(p-methylphenyl)-2-oxobutyrateHCID 13454543tert-butyl 3(R)-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetate

Product 1

HCID 54104533tert-butyl 3(R)-[1-ethoxycarbonyl-3-(p-tolyl)propyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetateYield 18%

Reagents, catalysts & solvents 2

HCID 178418390HCID 178418390, compoundCatalystHCID 176Acetic AcidSolvent

Procedure

A mixture of 50 ml of ethanol, 1 g of tert-butyl 3(R)-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetate, 0.4 g of acetic acid, 3.6 g of ethyl 4-(p-methylphenyl)-2-oxobutyrate and 5 g of molecular sieve 4A is stirred at room temperature for 1 hour, and the mixture is subjected to catalytic reduction over 0.5 g of 5% palladium carbon, at ordinary temperature and at atmospheric pressure. After 7 hours, the catalyst is filtered off and the mixture is concentrated. The residue is treated with oxalic acid in a manner similar to that described in Example 1. The resulting oil is purified by silica gel column chromatography to give 0.3 g of tert-butyl 3(R)-[1-ethoxycarbonyl-3-(p-tolyl)propyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetate as colorless oil. This product is a mixture of two diastereomers (about 1:1).

Workup

  1. waitAfter 7 hours
  2. filtrationthe catalyst is filtered off
  3. concentrationthe mixture is concentrated
  4. additionThe residue is treated with oxalic acid in a manner similar to
  5. customThe resulting oil is purified by silica gel column chromatography

Sources & evidence

ORD record
ord-5bf1f2c8f97040ecaca7edb1151ced6b
Source dataset
uspto-grants-1986_01
Patent number
US04564612

Reaction notes

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