Dimethyl Sulfoxide → tert-butyl (1R,4S)-4-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)-3-formylcyclohexylcarbamate

HRID 1171586Notes

Reaction equation

HRID 1171586 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH2:11]([O:18][C:19]([NH:21][C@H:22]1[CH2:26][CH2:25][N:24]([C@H:27]2[CH2:32][CH2:31][C@@H:30]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH2:29][C@H:28]2[CH2:41][OH:42])[C:23]1=[O:43])=[O:20])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C>ClCCl>[CH2:11]([O:18][C:19]([NH:21][C@H:22]1[CH2:26][CH2:25][N:24]([C@H:27]2[CH2:32][CH2:31][C@@H:30]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:38])([CH3:39])[CH3:37])[CH2:29][CH:28]2[CH:41]=[O:42])[C:23]1=[O:43])=[O:20])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 68767819tert-butyl (1R,3R,4S)-4-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)-3-(hydroxymethyl)cyclohexylcarbamate

Product 1

HCID 86596900tert-butyl (1R,4S)-4-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)-3-formylcyclohexylcarbamateYield 100.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of oxalyl chloride (2.0 M in dichloromethane, 370 μL, 735 μmol) in dichloromethane (1.6 mL) was stirred at −78° C. Dimethyl sulfoxide (108 μL, 1.51 mmol) was added dropwise over about 2 min, and the mixture was stirred for 35 min. A solution of tert-butyl (1R,3R,4S)-4-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)-3-(hydroxymethyl)cyclohexylcarbamate (219 mg, 475 μmol, See Example 4a, Step 1) in dichloromethane (1.5 mL) was added and the solution was stirred at −78° C. for 65 min. Triethylamine (215 μL, 1.54 mmol) was added, and after 10 min the mixture was warmed to 0° C. and stirred for 2 h. The mixture was diluted with dichloromethane, washed with saturated aqueous ammonium chloride, then with water, and was dried over sodium sulfate and concentrated under vacuum to provide tert-butyl (1R,4S)-4-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)-3-formylcyclohexylcarbamate as a tan glassy foam (220 mg). MS found: (M+Na)=482.37.

Workup

  1. stirringthe solution was stirred at −78° C. for 65 min
  2. stirringstirred for 2 h
  3. washwashed with saturated aqueous ammonium chloride
  4. dry with materialwith water, and was dried over sodium sulfate
  5. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-d0a07c7b28f545d299103ef43645f0f3
Source dataset
uspto-grants-2010_11
Patent number
US07829571B2

Reaction notes

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