Acetic Acid → 5-t-butoxycarbonylmethyl-3-(1-ethoxycarbonyl-3-phenylpropylamino)-2-phenyl-2,3-dihydro-1,5-benzothiazepin-4(5H)-one

HRID 1719130Notes

Reaction equation

HRID 1719130 reaction equation
[NH2:1][CH:2]1[C:8](=[O:9])[N:7]([CH2:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C:6]2[CH:18]=[CH:19][CH:20]=[CH:21][C:5]=2[S:4][CH:3]1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.[CH2:28]([CH2:35][C:36](=O)[C:37]([O:39][CH2:40][CH3:41])=[O:38])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.C(O)(=O)C.[BH]C#N.[Na]>C(O)C>[C:14]([O:13][C:11]([CH2:10][N:7]1[C:6]2[CH:18]=[CH:19][CH:20]=[CH:21][C:5]=2[S:4][CH:3]([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:2]([NH:1][CH:36]([C:37]([O:39][CH2:40][CH3:41])=[O:38])[CH2:35][CH2:28][C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:8]1=[O:9])=[O:12])([CH3:17])([CH3:16])[CH3:15]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 562087Ethyl alpha-oxobenzenebutanoateHCID 135331903-amino-5-t-butoxycarbonylmethyl-2-phenyl-2,3-dihydro-1,5-benzothiazepin-4(5H)-oneHCID 131714321Sodium boron cyanide hydride

Product 1

HCID 202675745-t-butoxycarbonylmethyl-3-(1-ethoxycarbonyl-3-phenylpropylamino)-2-phenyl-2,3-dihydro-1,5-benzothiazepin-4(5H)-oneYield 92.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
40 °C

Procedure

1.2 g of the compound obtained in Example 20 was mixed with 2.0 g of ethyl benzylpyruvate, 20 ml of ethanol and 1 ml of acetic acid and dissolved therein by warming to 40° C. The resulting reaction mixture was stirred for 3 hours. Thereafter, a solution of 400 mg of sodium boron cyanide hydride in 10 ml of ethanol was slowly added dropwise to the reaction mixture, which was then allowed to stand overnight. After the solvent was distilled off under reduced pressure, the residue was dissolved in ethyl acetate. The resulting solution was washed with water, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The concentrate was fractionated and purified by silica gel column chromatography using a 9:1 mixture of benzene and ethyl acetate as the eluent. Thus, there was obtained 1.66 g of the desired compound.

Workup

  1. dissolutiondissolved
  2. customThe resulting reaction mixture
  3. waitto stand overnight
  4. distillationAfter the solvent was distilled off under reduced pressure
  5. dissolutionthe residue was dissolved in ethyl acetate
  6. washThe resulting solution was washed with water
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. custompurified by silica gel column chromatography
  10. additiona 9:1 mixture of benzene and ethyl acetate as the eluent

Sources & evidence

ORD record
ord-c734490792d44567b583b97fe3003f4e
Source dataset
uspto-grants-1985_09
Patent number
US04539150

Reaction notes

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