Lithiumtriethylborohydride → HCID 23582403, compound

HRID 238803Notes

Reaction equation

HRID 238803 reaction equation
[F:1][C:2]1[CH:47]=[CH:46][C:5]([C:6]([NH:8][C@:9]([C:35]2[CH:40]=[CH:39][C:38]([F:41])=[C:37]([C:42]([F:45])([F:44])[F:43])[CH:36]=2)([C:21]2[CH:26]=[C:25]([O:27][C:28]([F:33])([F:32])[CH:29]([F:31])[F:30])[CH:24]=[C:23]([F:34])[CH:22]=2)[CH2:10][C:11]2[CH:20]=[CH:19][C:14]([C:15](OC)=[O:16])=[CH:13][CH:12]=2)=[O:7])=[CH:4][C:3]=1[C:48]([F:51])([F:50])[F:49].C([BH-](CC)CC)C.[Li+]>C1COCC1>[F:1][C:2]1[CH:47]=[CH:46][C:5]([C:6]([NH:8][C@:9]([C:35]2[CH:40]=[CH:39][C:38]([F:41])=[C:37]([C:42]([F:43])([F:44])[F:45])[CH:36]=2)([C:21]2[CH:26]=[C:25]([O:27][C:28]([F:33])([F:32])[CH:29]([F:30])[F:31])[CH:24]=[C:23]([F:34])[CH:22]=2)[CH2:10][C:11]2[CH:20]=[CH:19][C:14]([CH2:15][OH:16])=[CH:13][CH:12]=2)=[O:7])=[CH:4][C:3]=1[C:48]([F:51])([F:50])[F:49]

Participants

4

Reactant 2

HCID 23664628LithiumtriethylborohydrideHCID 59459363HCID 59459363, compound

Product 1

HCID 23582403HCID 23582403, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of (R)-methyl 4-(2-(4-fluoro-3-(trifluoromethyl)benzamido)-2-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)ethyl)benzoate prepared as described in Procedure 96, 97, 98, 56 and 57 (29 mg, 0.039 mmol) in THF at −78° C. was added a solution of lithium triethylborohydride (1.0 M in THF, 0.5 mL, 0.5 mmol). The resulting mixture was stirred at −78° C. for 1.5 h. The reaction was quenched by addition of 1 N NaOH (1 mL) and the aqueous layer was extracted with EtOAc (15 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by ISCO (12 g silica gel column, 0-50% EtOAc/hexane over min) to yield (R)-4-fluoro-N-(1-(4-fluoro-3-(trifluoromethyl)phenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-(4-(hydroxymethyl)phenyl)ethyl)-3-(trifluoromethyl)benzamide (Example 299) as a colorless film (22 mg, 79% yield). LCMS: RT=2.10 min [M+H] 714.31 (Phenomenex Luna C18 4.6×30 mm column, eluting with 10-90% MeOH/H2O containing 0.1% TFA, 2 min gradient, flow rate 5 mL/min, wavelength 220 nm); HPLC: RT=4.0 min (Phenomenex Luna C18 4.6×50 mm column, eluting with 10-90% MeOH/H2O containing 0.2% PPA, flow rate 4 mL/min, wavelength 220 nm); 1H NMR (400 MHz, CDCl3) δ ppm 7.98-7.80 (1H, m), 7.85-7.89 (1H, m), 7.39-7.43 (3H, m), 7.31 (1H, t, J=9.23 Hz), 7.19-7.27 (1H, m), 6.99 (1H, d, J=8.79 Hz), 6.76-6.83 (5H, m), 5.89 (1H, t, J=53.0 Hz), 4.16 (1H, d, J=13.18 Hz), 4.02 (1H, d, J=13.18 Hz).

Workup

  1. customThe reaction was quenched by addition of 1 N NaOH (1 mL)
  2. extractionthe aqueous layer was extracted with EtOAc (15 mL)
  3. dry with materialThe organic layer was dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by ISCO (12 g silica gel column, 0-50% EtOAc/hexane over min)

Sources & evidence

ORD record
ord-ca56a00bf3c9445e989023de58e2c395
Source dataset
uspto-grants-2014_02
Patent number
US08642576B2

Reaction notes

Loading…