Vinyl Acetate → HCID 59458689, compound

HRID 238808Notes

Reaction equation

HRID 238808 reaction equation
[F:1][C:2]1[CH:40]=[CH:39][C:5]([C:6]([NH:8][C@:9]([C:31]2[CH:36]=[CH:35][C:34]([F:37])=[C:33]([OH:38])[CH:32]=2)([C:17]2[CH:22]=[C:21]([O:23][C:24]([F:29])([F:28])[CH:25]([F:27])[F:26])[CH:20]=[C:19]([F:30])[CH:18]=2)[CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:7])=[CH:4][C:3]=1[C:41]([F:44])([F:43])[F:42].C([O-])([O-])=O.[Na+].[Na+].[C:51](OC=C)(=O)[CH3:52]>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:40]=[CH:39][C:5]([C:6]([NH:8][C@:9]([C:31]2[CH:36]=[CH:35][C:34]([F:37])=[C:33]([O:38][CH:51]=[CH2:52])[CH:32]=2)([C:17]2[CH:22]=[C:21]([O:23][C:24]([F:28])([F:29])[CH:25]([F:27])[F:26])[CH:20]=[C:19]([F:30])[CH:18]=2)[CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:7])=[CH:4][C:3]=1[C:41]([F:44])([F:43])[F:42]

Participants

5

Reactant 3

HCID 7904Vinyl AcetateHCID 10340Sodium CarbonateHCID 23582864HCID 23582864, compound

Product 1

HCID 59458689HCID 59458689, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (R)-4-fluoro-N-(1-(4-fluoro-3-hydroxyphenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenyethyl)-3-(trifluoromethyl)benzamide (Example 264, 100 mg, 0.158 mmol) in toluene (0.2 ml) was added Na2CO3 (25 mg, 0.235 mmol) and catalystical amount of [Ir(cod)Cl]2 (2 mg), followed by vinyl acetate (68 mg, 0.79 mmol). The reaction mixture was stirred at 100° C. for 16 h. The resulting mixture was filtered and the solid was washed with CH2Cl2. The CH2Cl2 layer was washed with 1 N NaOH, H2O and dried over Na2SO4 and filtered. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column using 0 to 60% EtOAc in hexane to afford (R)-4-fluoro-N-(1-(4-fluoro-3-(vinyloxy)phenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-3-(trifluoromethyl)benzamide eluting out at 20% EtOAc in hexane as colorless oil (80 mg, 77%). LCMS: RT=2.237 min [M+H] 658.3 (2 min Phenomenex Luna C18 column, 4.6×30 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm. NMR: 400 MHz 1H (CD3OD) ppm 3.87 (d, J=12.74 Hz, 1H), 4.05-4.15 (m, 1H), 4.35 (dd, J=5.93, 1.98 Hz, 1H), 4.55 (dd, J=13.84, 1.98 Hz, 1H), 6.12-6.41 (m, 1H), 6.48 (dd, J=13.62, 6.15 Hz, 1H), 6.72 (d, J=7.03 Hz, 2H), 6.87-7.24 (m, 9H), 7.37-7.51 (m, 1H), 7.88-8.04 (m, 2H).

Workup

  1. filtrationThe resulting mixture was filtered
  2. washthe solid was washed with CH2Cl2
  3. washThe CH2Cl2 layer was washed with 1 N NaOH, H2O
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customThe solvent was evaporated under reduced pressure
  7. customthe residue was purified by silica gel column

Sources & evidence

ORD record
ord-0b4fbc2c29384355a34301c60981ba47
Source dataset
uspto-grants-2014_02
Patent number
US08642576B2

Reaction notes

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