Dimethyl Sulfoxide → N-[(3-Chloro-1-Methylindole-2-Carbonyl)Valinyl]-3-Amino-4-Oxo-5-Fluoropentanoic Acid, t-Butyl Ester

HRID 634926Notes

Reaction equation

HRID 634926 reaction equation
CS(C)=O.C(Cl)(=O)C([Cl:8])=O.[CH3:11][N:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[C:13]1[C:21]([NH:23][C@H:24]([C:28]([NH:30][CH:31]([CH:40]([OH:43])[CH2:41][F:42])[CH2:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])=[O:29])[CH:25]([CH3:27])[CH3:26])=[O:22].C(N(CC)CC)C>C(Cl)Cl>[Cl:8][C:14]1[C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[N:12]([CH3:11])[C:13]=1[C:21]([NH:23][C@H:24]([C:28]([NH:30][CH:31]([C:40](=[O:43])[CH2:41][F:42])[CH2:32][C:33]([O:35][C:36]([CH3:38])([CH3:37])[CH3:39])=[O:34])=[O:29])[CH:25]([CH3:26])[CH3:27])=[O:22]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 69986607N-[(1-methylindole-2-carbonyl)valinyl]-3-amino-4-hydroxy-5-fluoropentanoic Acid T-Butyl Ester

Product 1

HCID 86586079N-[(3-Chloro-1-Methylindole-2-Carbonyl)Valinyl]-3-Amino-4-Oxo-5-Fluoropentanoic Acid, t-Butyl EsterYield 71.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

DMSO (0.06 mL, 0.9 mmol) was added to a solution of oxalyl chloride (0.14 mL, 2.0 M, 0.28 mmol, in 4 ml, of methylene chloride) and the solution was then stirred for 10 minutes under a nitrogen atmosphere at −78° C. A solution of N-[(1-methylindole-2-carbonyl) valinyl]-3-amino-4-hydroxy-5-fluoropentanoic acid, t-butyl ester (85 mg, 0.18 mmol) in dry methylene chloride (1 mL), was added dropwise to the reaction mixture and the mixture was stirred for 15 minutes at −78° C. Triethylamine (0.15 ml, 1.08 mmol) was added dropwise to the reaction mixture and the mixture was stirred for 10 minutes at −78° C. and then was allowed to warm to room temperature. The reaction mixture was partitioned between ethyl acetate and 5% KHSO4 solution and the aqueous layer was back-extracted with ethyl acetate. The combined ethyl acetate solutions were washed with 5% KHSO4 solution and brine, dried over sodium sulfate, and concentrated to give a brown foam. The foam was triturated with ether to afford the title product as a light brown powder (64 mg). MS for C24H31ClFN3O5: (MH)−=494/496.

Workup

  1. stirringthe mixture was stirred for 15 minutes at −78° C
  2. stirringthe mixture was stirred for 10 minutes at −78° C.
  3. temperatureto warm to room temperature
  4. customThe reaction mixture was partitioned between ethyl acetate and 5% KHSO4 solution
  5. extractionthe aqueous layer was back-extracted with ethyl acetate
  6. washThe combined ethyl acetate solutions were washed with 5% KHSO4 solution and brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customto give a brown foam
  10. customThe foam was triturated with ether

Sources & evidence

ORD record
ord-d0a6448938c74c2ca439f53115afc8aa
Source dataset
uspto-grants-2001_02
Patent number
US06184244B2

Reaction notes

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