Sodium borohydride → HCID 68993996, compound

HRID 578789Notes

Reaction equation

HRID 578789 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[C:11]([C:16]([CH3:28])([CH3:27])[C:17]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[O:25][CH3:26])=[O:18])[CH:12]=[CH:13][C:14]=1[F:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+]>O1CCCC1.O>[C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[C:11]([C:16]([CH3:28])([CH3:27])[CH:17]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[O:25][CH3:26])[OH:18])[CH:12]=[CH:13][C:14]=1[F:15])=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 68996014HCID 68996014, compound

Product 1

HCID 68993996HCID 68993996, compoundYield 91.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 2-[3-(tert-butoxycarbonylamino)-4-fluorophenyl]-1-(2-methoxyphenyl)-2-methyl-1-propanone (0.59 g) in tetrahydrofuran (7.5 mL)-water (0.75 mL) was added sodium borohydride (0.17 g), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with water, and the resulting mixture was extracted with ethyl acetate. The extract was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=4/1) to give 2-[3-(tert -butoxycarbonylamino)-4-fluorophenyl]-1-(2-methoxyphenyl)-2-methyl-1-propanol (0.54 g). This material was dissolved in ethanol (8 mL)-tetrahydrofuran (3 mL). To the solution were added 2 mol/L hydrochloric acid (0.2 mL) and 10% palladium-carbon powder (0.27 g), and the mixture was stirred at room temperature under a hydrogen atmosphere for 5 hours. To the reaction mixture was added sodium hydrogen carbonate, and the mixture was stirred for 10 minutes. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=7/1) to give 2-[3-(tert -butoxycarbonylamino)-4-fluorophenyl]-1-(2-methoxyphenyl)-2-methylpropane (0.15 g). To this material was added hydrochloric acid (4 mol/L ethyl acetate solution, 3 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into a saturated aqueous sodium hydrogen carbonate solution, and the resulting mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to give the title compound (0.11 g).

Workup

  1. extractionthe resulting mixture was extracted with ethyl acetate
  2. washThe extract was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was removed under reduced pressure
  5. customthe residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=4/1)

Sources & evidence

ORD record
ord-db09c0345fc3449f97e292b558a4da4f
Source dataset
uspto-grants-2015_05
Patent number
US09040693B2

Reaction notes

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