Ethyl Acetate → Methyl 2-[(tert-butoxycarbonyl)amino]-4-(4-chlorophenyl)-5-oxohexanoate

HRID 448226

Reaction equation

HRID 448226 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:12]([O:14][CH3:15])=[O:13])[CH2:10]I)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][C:24](=[O:26])[CH3:25])=[CH:19][CH:18]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CCOC(C)=O>CN(C)C=O>[C:1]([O:5][C:6]([NH:8][CH:9]([CH2:10][CH:23]([C:20]1[CH:21]=[CH:22][C:17]([Cl:16])=[CH:18][CH:19]=1)[C:24](=[O:26])[CH3:25])[C:12]([O:14][CH3:15])=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 796991-(p-Chlorophenyl)acetoneHCID 10903591methyl (2R)-2-(((tert-butoxy)carbonyl)amino)-3-iodopropanoate

Product 1

HCID 68747752Methyl 2-[(tert-butoxycarbonyl)amino]-4-(4-chlorophenyl)-5-oxohexanoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of methyl N-(tert-butoxycarbonyl)-3-iodo-L-alaninate (215 g, 652 mmol) and 4-chlorophenylacetone (100 g, 593 mmol) in N,N-dimethylformamide (1.5 L) was added cesium carbonate (483 g, 1.48 mol) at room temperature. After 4 h, the mixture was then added to a stirring solution of pH 7 buffer and EtOAc. The aqueous layer was extracted with EtOAc and the combined organics were washed with pH 7 buffer, dried over sodium sulfate, filtered and concentrated. The crude product was purified by silica gel chromatography (10% ethyl acetate/heptane→>30% ethyl acetate/heptane) to provide the title compound as a mixture of diastereomers. MS: m/z=392.1 (M+Na).

Workup

  1. additionthe mixture was then added to a stirring solution of pH 7 buffer
  2. extractionThe aqueous layer was extracted with EtOAc
  3. washthe combined organics were washed with pH 7 buffer
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by silica gel chromatography (10% ethyl acetate/heptane→>30% ethyl acetate/heptane)

Sources & evidence

ORD record
ord-7ed7c73a25a546838094850d1fdcb9a0
Source dataset
uspto-grants-2013_07
Patent number
US08481556B2

Linked notes

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