Triethylamine → 3-Acetylsulfanyl-2-(6-tert-butoxycarbonylamino-pyridin-3-ylmethyl)-butyric acid ethyl ester

HRID 1789873Notes

Reaction equation

HRID 1789873 reaction equation
[S:1]1C=CC=C1CC(O)=O.CCN(CC)CC.[CH2:17]([O:19][C:20](=[O:41])[C:21]([CH2:26][C:27]1[CH:28]=[N:29][C:30]([NH:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])=[CH:31][CH:32]=1)=[C:22]([CH2:24]C)C)[CH3:18].[CH3:42][CH2:43][O:44]C(C)=O>>[CH2:17]([O:19][C:20](=[O:41])[CH:21]([CH2:26][C:27]1[CH:28]=[N:29][C:30]([NH:33][C:34]([O:36][C:37]([CH3:38])([CH3:39])[CH3:40])=[O:35])=[CH:31][CH:32]=1)[CH:22]([S:1][C:43](=[O:44])[CH3:42])[CH3:24])[CH3:18]

Participants

5

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 159702-Thiopheneacetic acid2×HCID 57028003Ethyl 2-(6-tert-butoxycarbonylamino-pyridin-3-ylmethyl)-but-2-enoic acid ethyl ester

Product 1

HCID 537302483-Acetylsulfanyl-2-(6-tert-butoxycarbonylamino-pyridin-3-ylmethyl)-butyric acid ethyl ester

Procedure

To thiolacetic acid (15 mL) were added Et3N (1.5 g, 14.8 mmol) and ethyl 2-(6-tert-butoxycarbonylamino-pyridin-3-ylmethyl)-but-2-enoic acid ethyl ester (920 mg, 2.9 mmol) at room temperature. The reaction mixture was stirred at 40-45° C. for 7 days (additional thiolacetic acid (1.5 mL) was added to the reaction mixture every two days). The reaction mixture was cooled to room temperature and then diluted with EtOAc (50 mL). The organic layer was separated, washed with sat. NaHCO3, brine and dried. The combined organic layers were concentrated under reduced pressure. The crude was purified subsequently by three chromatography columns (CH2Cl2, EtOAc/hexane, 1:5 and acetone/hexane, 1:8) to afford 3-acetylsulfanyl-2-(6-tert-butoxycarbonylamino-pyridin-3-ylmethyl)-butyric acid ethyl ester as a diastereometric mixture (780 mg, 68%). The diastereomeric mixture was separated using preparative chiral chromatography according to the procedure described below to give the four isomers 3-acetylsulfanyl-2-(6-tert-butoxycarbonylamino-pyridin-3-ylmethyl)-butyric acid ethyl ester/A, 3-acetylsulfanyl-2-(6-tert-butoxycarbonylamino-pyridin-3-ylmethyl)-butyric acid ethyl ester/B, 3-acetylsulfanyl-2-(6-tert-butoxycarbonylamino-pyridin-3-ylmethyl)-butyric acid ethyl ester/C and 3-acetylsulfanyl-2-(6-tert-butoxycarbonylamino-pyridin-3-yl methyl)-butyric acid ethyl ester/D.

Workup

  1. additionwas added to the reaction mixture every two days)
  2. customThe organic layer was separated
  3. washwashed with sat. NaHCO3, brine
  4. customdried
  5. concentrationThe combined organic layers were concentrated under reduced pressure
  6. customThe crude was purified subsequently by three chromatography columns (CH2Cl2, EtOAc/hexane, 1:5 and acetone/hexane, 1:8)

Sources & evidence

ORD record
ord-97eb620169274daea02aff9f956b1368
Source dataset
uspto-grants-2006_07
Patent number
US07071175B1

Reaction notes

Loading…