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

HRID 908599Notes

Reaction equation

HRID 908599 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17](=[S:19])[NH2:18])[CH2:13][C@@H:12]1[C:20](=[O:32])[NH:21][CH2:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29][CH2:30][CH3:31])=[CH:25][CH:24]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:33]([O:37][C:38](=[O:44])[CH:39](Br)[C:40](=O)[CH3:41])([CH3:36])([CH3:35])[CH3:34]>C(#N)C>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]2[S:19][C:39]([C:38]([O:37][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:44])=[C:40]([CH3:41])[N:18]=2)[CH2:13][C@@H:12]1[C:20](=[O:32])[NH:21][CH2:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29][CH2:30][CH3:31])=[CH:25][CH:24]=1)=[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 59703710(R)-2-(4-propyl-benzylcarbamoyl)-4-thiocarbamoyl-piperazine-1-carboxylic acid benzyl ester

Product 1

HCID 59703739(R)-4-(5-tert-butoxycarbonyl-4-methyl-thiazol-2-yl)-2-(4-propyl-benzylcarbamoyl)-piperazine-1-carboxylic acid benzyl esterYield 65.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of the compound (1.51 g) obtained in Step 4 and 2-bromo-3-oxobutyric acid tert-butyl ester (1.58 g) in acetonitrile (15 ml) was stirred at 80° C. for 15 min. The reaction mixture was concentrated under reduced pressure, and the residue was partitioned by adding ethyl acetate and water. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtrated, and concentrated under reduced pressure. The residue was purified by column chromatography (ethyl acetate:n-hexane=1:2-2:3) to give the title compound (1.29 g).

Workup

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

Sources & evidence

ORD record
ord-d924d7375ad14da59bd1645cf9a370ae
Source dataset
uspto-grants-2011_09
Patent number
US08017612B2

Reaction notes

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