2-Bromo-3-oxobutyric acid tert-butyl ester → (R)-4-(5-tert-butoxycarbonyl-4-methyl-thiazol-2-yl)-1-(4-trifluoromethoxy-benzenesulfonyl)-piperazine-2-carboxylic acid benzyl ester

HRID 908593Notes

Reaction equation

HRID 908593 reaction equation
[CH2:1]([O:8][C:9]([C@H:11]1[CH2:16][N:15]([C:17](=[S:19])[NH2:18])[CH2:14][CH2:13][N:12]1[S:20]([C:23]1[CH:28]=[CH:27][C:26]([O:29][C:30]([F:33])([F:32])[F:31])=[CH:25][CH:24]=1)(=[O:22])=[O:21])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:34]([O:38][C:39](=[O:45])[CH:40](Br)[C:41](=O)[CH3:42])([CH3:37])([CH3:36])[CH3:35]>C(#N)C>[CH2:1]([O:8][C:9]([C@H:11]1[CH2:16][N:15]([C:17]2[S:19][C:40]([C:39]([O:38][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:45])=[C:41]([CH3:42])[N:18]=2)[CH2:14][CH2:13][N:12]1[S:20]([C:23]1[CH:24]=[CH:25][C:26]([O:29][C:30]([F:33])([F:31])[F:32])=[CH:27][CH:28]=1)(=[O:21])=[O:22])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 108899382-Bromo-3-oxobutyric acid tert-butyl esterHCID 59703783(R)-4-thiocarbamoyl-1-(4-trifluoromethoxy-benzenesulfonyl)-piperazine-2-carboxylic acid benzyl ester

Product 1

HCID 59703728(R)-4-(5-tert-butoxycarbonyl-4-methyl-thiazol-2-yl)-1-(4-trifluoromethoxy-benzenesulfonyl)-piperazine-2-carboxylic acid benzyl esterYield 67.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of the compound (2.12 g) obtained in Step 4 and 2-bromo-3-oxobutyric acid tert-butyl ester (2.0 g) in acetonitrile (20 ml) was stirred at 80° C. for 30 min. The reaction mixture was concentrated under reduced pressure, and the residue was partitioned by adding ethyl acetate and saturated aqueous sodium carbonate solution. The organic layer was washed successively with saturated aqueous sodium carbonate solution and saturated brine, dried over anhydrous sodium sulfate, filtrated, and concentrated under reduced pressure. The residue was purified by column chromatography (ethyl acetate:n-hexane=1:2) to give the title compound (1.82 g).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customthe residue was partitioned
  3. additionby adding ethyl acetate and saturated aqueous sodium carbonate solution
  4. washThe organic layer was washed successively with saturated aqueous sodium carbonate solution and saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltrated
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by column chromatography (ethyl acetate:n-hexane=1:2)

Sources & evidence

ORD record
ord-45fb635700ab4f15a82c542997a23d1b
Source dataset
uspto-grants-2011_09
Patent number
US08017612B2

Reaction notes

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