Sodium hydride → Methyl 2-[(tert-butoxycarbonyl)amino]-4-cyano-4-(2,3-difluorophenyl)butanoate

HRID 406554Notes

Reaction equation

HRID 406554 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][C:10]#[N:11].[H-].[Na+].[C:14]([O:18][C:19]([NH:21][C@@H:22]([C:25]([O:27][CH3:28])=[O:26])[CH2:23]I)=[O:20])([CH3:17])([CH3:16])[CH3:15].C(=O)(O)[O-].[Na+]>CN(C)C=O.O>[C:14]([O:18][C:19]([NH:21][CH:22]([CH2:23][CH:9]([C:10]#[N:11])[C:3]1[CH:4]=[CH:5][CH:6]=[C:7]([F:8])[C:2]=1[F:1])[C:25]([O:27][CH3:28])=[O:26])=[O:20])([CH3:17])([CH3:16])[CH3:15]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 5189682,3-DifluorophenylacetonitrileHCID 11416215(S)-Methyl 2-Boc-amino-3-iodopropionate

Product 1

HCID 68748709Methyl 2-[(tert-butoxycarbonyl)amino]-4-cyano-4-(2,3-difluorophenyl)butanoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (2,3-difluorophenyl)acetonitrile (18.6 g, 122 mmol) in N,N-dimethylformamide (243 mL) at 0° C. was added sodium hydride (60% dispersion in mineral oil) (4.37 g, 109 mmol). After 20 min, methyl N-(tert-butoxycarbonyl)-3-iodo-D-alaninate (20.0 g, 60.8 mmol) was added, and the resulting mixture stirred 50 min. Saturated aqueous sodium bicarbonate was added, and the mixture was warmed to ambient temperature. Water was added and the mixture was extracted with ethyl acetate (3×). The combined organic extracts were washed with water (3×), brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% hexanes→20% hexanes/ethyl acetate) gave the title compound. MS: m/z=377.3 (M+Na).

Workup

  1. extractionthe mixture was extracted with ethyl acetate (3×)
  2. washThe combined organic extracts were washed with water (3×), brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by silica gel chromatography (100% hexanes→20% hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-13767588ff554b1dbd6c4012c08e4c1a
Source dataset
uspto-grants-2014_06
Patent number
US08754096B2

Reaction notes

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