Sodium Methoxide → HCID 59458785, compound

HRID 1874257Notes

Reaction equation

HRID 1874257 reaction equation
Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C@@:9]([NH:31][C:32](=[O:44])[C:33]2[CH:38]=[CH:37][C:36]([F:39])=[C:35]([C:40]([F:43])([F:42])[F:41])[CH:34]=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)=[CH:5][CH:4]=1.[CH3:45][O-:46].[Na+]>CO>[F:39][C:36]1[CH:37]=[CH:38][C:33]([C:32]([NH:31][C@@:9]([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)([C:6]2[CH:5]=[CH:4][C:3]([CH2:2][O:46][CH3:45])=[CH:8][CH:7]=2)[CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:44])=[CH:34][C:35]=1[C:40]([F:43])([F:41])[F:42]

Participants

4

Reactant 2

HCID 10942334Sodium MethoxideHCID 59458878HCID 59458878, compound

Product 1

HCID 59458785HCID 59458785, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(R)—N-(1-(4-(bromomethyl)phenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-4-fluoro-3-(trifluoromethyl)benzamide (prepared as described in Procedure 3, 4, 5, 6, 7, 56, 57, 100 and 32, 24 mg, 0.035 mmol) was dissolved in 0.5 mL of methanol. To this solution was added sodium methoxide (25% by wt, 0.5 mL) and the reaction mixture was stirred for 40 min. The reaction was quenched with 1.0 M HCl and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, filtered and concentrated. The resulting oil was purified by flash chromatography (4 g silica gel column, 0-100% EtOAc/hexane gradient over 11 min., flow rate 18 mL/min) to provide (R)-4-fluoro-N-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-(methoxymethyl)phenyl)-2-phenylethyl)-3-(trifluoromethyl)benzamide (Example 321) as a white solid (15 mg, 67% yield). LC/MS: RT=1.62 min [M+H] 642 (Chromolith Performance 18e 4.6×100 mm column, 50-90% acetonitrile, water with 0.1% trifluoroacetic acid gradient over 2 min, 5 mL/min); 1H NMR (400 MHz, CDCl3) ppm 7.91 (1H, d, J=7.15 Hz), 7.77-7.87 (1H, m), 7.08-7.44 (7H, m), 6.97-7.05 (2H, m), 6.92 (1H, d, J=8.79 Hz), 6.66-6.75 (3H, m), 5.87 (1H, tt, JHH=2.75 Hz, JHF=53 Hz), 4.47 (2H, s), 4.09 (1H, d, J=13.2 Hz), 3.81 (1H, d, J=13.2 Hz), 3.42 (3H, s).

Workup

  1. customThe reaction was quenched with 1.0 M HCl
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic layer was dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting oil was purified by flash chromatography (4 g silica gel column, 0-100% EtOAc/hexane gradient over 11 min., flow rate 18 mL/min)

Sources & evidence

ORD record
ord-a4185b41ab314021b165dd72dbff1ede
Source dataset
uspto-grants-2012_11
Patent number
US08304403B2

Reaction notes

Loading…