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

HRID 2120636Notes

Reaction equation

HRID 2120636 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.[C:11]1([N:17]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=[C:18]2[C:26]([NH:28][C@H:29]([C:33]([NH:35][CH:36]([CH:45]([OH:48])[CH2:46][F:47])[CH2:37][C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])=[O:34])[CH:30]([CH3:32])[CH3:31])=[O:27])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(N(CC)CC)C>C(Cl)Cl>[C:11]1([N:17]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=[C:18]2[C:26]([NH:28][C@H:29]([C:33]([NH:35][CH:36]([C:45](=[O:48])[CH2:46][F:47])[CH2:37][C:38]([O:40][C:41]([CH3:42])([CH3:44])[CH3:43])=[O:39])=[O:34])[CH:30]([CH3:31])[CH3:32])=[O:27])[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 86584007N-[(1-Phenylindole-2-Carbonyl)Valinyl]-3-Amino-4-Hydroxy-5-Fluoropentanoic Acid, t-Butyl Ester

Product 1

HCID 86584008N-[(1-Phenylindole-2-Carbonyl)Valinyl]-3-Amino-4-Oxo-5-Fluoropentanoic Acid, t-Butyl Ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

DMSO (0.13 mL, 1.9 mmol) was added to a methylene chloride solution of oxalyl chloride (0.29 mL, 2.0 M, 0.58 mmol in 4 mL of methylene chloride), and the resultant solution was stirred for 10 minutes under a nitrogen atmosphere at 78° C. A methylene chloride solution of N-[(1-phenylindole-2-carbonyl)valinyl]-3-amino-4-hydroxy-5-fluoropentanoic acid, t-butyl ester (200 mg, 0.38 mmol in 2 mL of dry methylene chloride) was added dropwise and resulting mixture stirred for 15 minutes at −78° C. Triethylamine (0.30 mL, 2.1 mmol) was added dropwise to the mixture, and the resultant mixture was stirred for 10 minutes at −78° C., 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 crude product. The crude product was triturated to yield the title product as a slightly yellow powder (181 mg). TLC: (ethyl acetate/hexanes 1:1): Rf=0.43.

Workup

  1. customresulting mixture
  2. temperatureto warm to room temperature
  3. customThe reaction mixture was partitioned between ethyl acetate and 5% KHSO4 solution
  4. extractionthe aqueous layer was back-extracted with ethyl acetate
  5. washThe combined ethyl acetate solutions were washed with 5% KHSO4 solution and brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customto give a crude product
  9. customThe crude product was triturated

Sources & evidence

ORD record
ord-5d256d7acd14451a9233194209e8ced4
Source dataset
uspto-grants-2004_02
Patent number
US06693096B2

Reaction notes

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