Sodium Methoxide → HCID 59458785, compound

HRID 1712800Notes

Reaction equation

HRID 1712800 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-3fac4af77a5e465b9fc501896ea7702d
Source dataset
uspto-grants-2010_09
Patent number
US07790770B2

Reaction notes

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