Dimethylformamide → 4-{(S)-2-[(4-Benzyloxycarbonylmethoxy-quinoline-2-carbonyl)-amino]-4-tert-butoxycarbonyl-butyryl}-piperazine-1-carboxylic acid ethyl ester

HRID 1185436Notes

Reaction equation

HRID 1185436 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:37])[C@@H:13]([NH:23][C:24]([C:26]2[CH:35]=[C:34]([OH:36])[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[N:27]=2)=[O:25])[CH2:14][CH2:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:8][CH2:7]1)=[O:5])[CH3:2].CN(C=O)C.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:49]([O:56][C:57](=[O:60])[CH2:58]Br)[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1>O>[CH2:1]([O:3][C:4]([N:6]1[CH2:7][CH2:8][N:9]([C:12](=[O:37])[C@@H:13]([NH:23][C:24]([C:26]2[CH:35]=[C:34]([O:36][CH2:58][C:57]([O:56][CH2:49][C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)=[O:60])[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[N:27]=2)=[O:25])[CH2:14][CH2:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:10][CH2:11]1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 62576Benzyl bromoacetateHCID 178473385HCID 178473385, compound

Product 1

HCID 686029414-{(S)-2-[(4-Benzyloxycarbonylmethoxy-quinoline-2-carbonyl)-amino]-4-tert-butoxycarbonyl-butyryl}-piperazine-1-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of 6.2 g of 4-{(S)-4-tert-Butoxycarbonyl-2-[(4-hydroxy-quinoline-2-carbonyl)-amino]-butyryl}-piperazine-1-carboxylic acid ethyl ester 80 ml of DMF, 4.3 g of cesium carbonate and 2.5 g of Bromo-acetic acid benzyl ester was added and stirred for 2 h. Then, the reaction mixture was diluted with water and extracted with ethyl acetate (3×150 ml). The combined organic phases were dried over MgSO4 and the solvents were removed under reduced pressure. The crude product was purified by chromatography on silica gel eluting with a gradient of n-heptane/ethyl acetate. The fractions containing the product were combined and the solvent evaporated under reduced pressure. Yield: 4.4 g.

Workup

  1. extractionextracted with ethyl acetate (3×150 ml)
  2. dry with materialThe combined organic phases were dried over MgSO4
  3. customthe solvents were removed under reduced pressure
  4. customThe crude product was purified by chromatography on silica gel eluting with a gradient of n-heptane/ethyl acetate
  5. additionThe fractions containing the product
  6. customthe solvent evaporated under reduced pressure

Sources & evidence

ORD record
ord-99a7ab8d30034128a1583139712bd11a
Source dataset
uspto-grants-2014_03
Patent number
US08669266B2

Reaction notes

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