Cesium carbonate → Methyl N-(tert-butoxycarbonyl)-4-(2-fluorophenyl)-5-nitrilonorvalinate

HRID 448220Notes

Reaction equation

HRID 448220 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].C(=O)([O-])[O-].[Cs+].[Cs+].[F:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[CH2:29][C:30]#[N:31]>CN(C=O)C>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:12]([O:14][CH3:15])=[O:13])[CH2:10][CH:29]([C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[F:22])[C:30]#[N:31])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 10796Cesium carbonate2×HCID 67592Benzeneacetonitrile, 2-fluoro-HCID 11416215(S)-Methyl 2-Boc-amino-3-iodopropionate

Product 1

HCID 68748587Methyl N-(tert-butoxycarbonyl)-4-(2-fluorophenyl)-5-nitrilonorvalinate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of methyl N-(tert-butoxycarbonyl)-3-iodo-D-alaninate (5.00 g, 15.19 mmol) in DMF (20 mL) was added cesium carbonate (5.44 g, 16.71 mmol) and the mixture was stirred at 23° C. for 2 h. (2-Fluorophenyl)acetonitrile (5.87 mL, 45.6 mmol) and cesium carbonate (7.42 g, 22.8 mmol) were added and the resulting mixture was stirred for 1 h. The mixture was filtered and water was added to the filtrate. The mixture was extracted with ethyl acetate (3×). The combined organic extracts were washed with water (3×), brine, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography (0% ethyl acetate→50% ethyl acetate/hexane) gave the title compound as a racemic mixture of cis and trans diastereomers. MS: m/z=378.1 (M+CH3CN+1).

Workup

  1. additionwere added
  2. filtrationThe mixture was filtered
  3. additionwater was added to the filtrate
  4. extractionThe mixture was extracted with ethyl acetate (3×)
  5. washThe combined organic extracts were washed with water (3×), brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by silica gel chromatography (0% ethyl acetate→50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-fc71df34b62244f281b0fbc5267c06f4
Source dataset
uspto-grants-2013_07
Patent number
US08481556B2

Reaction notes

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