Potassium Carbonate → (2S)-3-(4-Cyano-3-fluorophenoxy)-2-hydroxy-2-methyl-N-(3-methyl-4-nitrophenyl)propionamide

HRID 133747Notes

Reaction equation

HRID 133747 reaction equation
[F:1][C:2]1[CH:9]=[C:8]([OH:10])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].Br[CH2:12][C@@:13]([OH:28])([CH3:27])[C:14]([NH:16][C:17]1[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[C:19]([CH3:26])[CH:18]=1)=[O:15].C([O-])([O-])=O.[K+].[K+]>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.C(C(C)=O)C>[C:4]([C:3]1[CH:6]=[CH:7][C:8]([O:10][CH2:27][C@@:13]([OH:28])([CH3:12])[C:14]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[C:19]([CH3:26])[CH:18]=2)=[O:15])=[CH:9][C:2]=1[F:1])#[N:5]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27346752-Fluoro-4-hydroxybenzonitrile2×HCID 59903827(2R)-3-bromo-2-hydroxy-2-methyl-N-(3-methyl-4-nitrophenyl)propionamide2×

Product 1

HCID 67525491(2S)-3-(4-Cyano-3-fluorophenoxy)-2-hydroxy-2-methyl-N-(3-methyl-4-nitrophenyl)propionamide

Reagents, catalysts & solvents 2

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 6569Methyl Ethyl KetoneSolvent

Procedure

(2S)-3-(4-Cyano-3-fluorophenoxy)-2-hydroxy-2-methyl-N-(3-methyl-4-nitrophenyl)propionamide was prepared as described in Example 3 starting from 2-fluoro-4-hydroxybenzonitrile and (2R)-3-bromo-2-hydroxy-2-methyl-N-(3-methyl-4-nitrophenyl)propionamide according to the following procedure. A solution of 2-fluoro-4-hydroxybenzonitrile (0.2 g, 1.4 mmol), (2R)-3-bromo-2-hydroxy-2-methyl-N-(3-methyl-4-nitrophenyl)propionamide (0.37 g, 1.2 mmol), K2CO3 (0.34 g, 2.5 mmol) and benzyltriethylammonium chloride (0.028 g, 0.1 mmol) in methyl ethyl ketone (40 ml) was refluxed for 5 hours. The mixture was cooled to the room temperature and evaporated. The residue was partitioned between ethyl acetate (50 ml) and water (50 ml) and the phases were separated. The organic phase was washed with 1 M Na2CO3 (4×20 ml) and water (1×20 ml), dried over Na2SO4 and evaporated. The crude product was purified by flash chromatography (eluent CH2Cl2). 1H NMR (DMSO-d6): 1.46 (3H, s), 2.53 (3H, s), 4.11 (1H, d, J=10.1 Hz), 4.371 (1H, d, J=10.1 Hz), 6.33 (1H, bs), 6.96 (1H, m), 7.18 (1H, m), 7.80 (1H, m), 7.88 (1H, dd, J=9.0 Hz and 2.1 Hz), 7.91 (1H, d, J=2.1 Hz), 8.03 (1H, d, J=9.0 Hz) 10.21 (1H, s).

Workup

  1. customevaporated
  2. customThe residue was partitioned between ethyl acetate (50 ml) and water (50 ml)
  3. customthe phases were separated
  4. washThe organic phase was washed with 1 M Na2CO3 (4×20 ml) and water (1×20 ml)
  5. dry with materialdried over Na2SO4
  6. customevaporated
  7. customThe crude product was purified by flash chromatography (eluent CH2Cl2)

Sources & evidence

ORD record
ord-8fcff69158e440ea97300fd272868f2d
Source dataset
uspto-grants-2008_06
Patent number
US07390923B2

Reaction notes

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