Lithiumtriethylborohydride → HCID 23582540, compound

HRID 1874291Notes

Reaction equation

HRID 1874291 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]([O:42][CH:43]([CH3:45])[CH3:44])[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]([O:42][CH:43]([CH3:45])[CH3:44])[CH:36]=2)([C:21]2[CH:26]=[C:25]([O:27][C:28]([F:32])([F:33])[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 59458976HCID 59458976, compound

Product 1

HCID 23582540HCID 23582540, compoundYield 78%

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-isopropoxyphenyl)-2-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)ethyl)benzoate (20 mg, 0.027 mmol) in THF (2 mL) at −78° C. was added a solution of lithium triethylborohydride (1.0 M in THF, 0.5 mL, 0.5 mmol). The reaction mixture was stirred at −78° C. for 1.5 h. The reaction was quenched by the addition of 1 N NaOH (1 mL) and diluted with EtOAc (15 mL). The organic portion was washed with sat. NaCl (2×10 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC (YMC Sunfire 5μ C18 30×100 mm column, eluting with 20-90% MeOH/H2O containing 0.1% TFA, 10 min gradient, flow rate 40 mL/min, wavelength 220 nm) to yield (R)-4-fluoro-N-(1-(4-fluoro-3-isopropoxyphenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-(4-(hydroxymethyl)phenyl)ethyl)-3-(trifluoromethyl)benzamide (Example 348, 13 mg, 78% yield) as a colorless film. LCMS: RT=2.17 min [M+H] 704.1 (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 7.91 (1H, d, J=6.59 Hz), 7.85-7.87 (1H, m) 7.26-7.31 (1H, m), 7.16 (2H, d, J=7.91 Hz), 6.93-7.05 (4H, m), 6.68-6.73 (3H, m), 6.60-6.66 (2H, m), 5.75-6.01 (1H, m), 4.64 (3 H, s), 4.35 (1H, m), 4.06 (1H, d, J=13.2 Hz), 3.74 (1H, d, J=13.2 Hz), 1.29 (3H, d, J=6.15 Hz), 1.26 (1H, s), 1.23 (3H, d, J=6.15 Hz).

Workup

  1. customThe reaction was quenched by the addition of 1 N NaOH (1 mL)
  2. additiondiluted with EtOAc (15 mL)
  3. washThe organic portion was washed with sat. NaCl (2×10 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by preparative HPLC (YMC Sunfire 5μ C18 30×100 mm column, eluting with 20-90% MeOH/H2O containing 0.1% TFA, 10 min gradient, flow rate 40 mL/min, wavelength 220 nm)

Sources & evidence

ORD record
ord-84ea29e652b5441aa720eada386b8efc
Source dataset
uspto-grants-2012_11
Patent number
US08304403B2

Reaction notes

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