Sodium borohydride → HCID 86703753, compound

HRID 1849868Notes

Reaction equation

HRID 1849868 reaction equation
[CH:1]1([C:4]2[C:5]([O:18][CH2:19][C:20]3([CH3:27])[CH2:25][CH2:24][C:23](=[O:26])[CH2:22][CH2:21]3)=[CH:6][C:7]([F:17])=[C:8]([CH:16]=2)[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:3][CH2:2]1.[BH4-].[Na+]>CO>[CH:1]1([C:4]2[C:5]([O:18][CH2:19][C:20]3([CH3:27])[CH2:25][CH2:24][CH:23]([OH:26])[CH2:22][CH2:21]3)=[CH:6][C:7]([F:17])=[C:8]([CH:16]=2)[C:9]([O:11][C:12]([CH3:13])([CH3:14])[CH3:15])=[O:10])[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 86703558HCID 86703558, compound

Product 1

HCID 86703753HCID 86703753, compoundYield 99%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of tert-butyl 5-cyclopropyl-2-fluoro-4-((1-methyl-4-oxocyclohexyl)-methoxy)benzoate (0.071 g, 0.190 mmol) in (3 mL) and methanol (1 mL) was added sodium borohydride (0.014 g, 0.38 mmol) and the reaction mixture was stirred 20 minutes at ambient temperature. The mixture was then quenched by addition of 1N hydrochloric acid until reaching pH=1. The mixture was extracted with dichloromethane (3×10 mL), the organic layers were combined and washed with brine (15 mL), dried over anhydrous magnesium sulfate, filtered and concentrated to afford tert-butyl 5-cyclopropyl-2-fluoro-4-((4-hydroxy-1-methylcyclohexyl)methoxy)benzoate (0.071 g, 99%) which was used directly for next step. To a solution of the previous compound in dichloromethane (3 mL) at −78° C. was added dropwise diethylaminosulfur trifluoride (0.15 g, 0.94 mmol) dissolved in dichloromethane (1 mL) and the reaction mixture was stirred 1 hour at −78° C., then slowly warmed up to ambient temperature during 2 hours. The mixture was then stirred at ambient temperature for a further 1 hour and then cooled down to −78° C. and quenched by addition of methanol (1 mL), followed by a saturated aqueous solution of sodium bicarbonate (2 mL). The mixture was warmed up to ambient temperature and extracted with dichloromethane (3×10 mL). The organic layers were combined and washed with brine (15 mL), dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by chromatography (0 to 30% ethyl acetate in hexanes) to give the title compound (0.048 g, 70%). 1H NMR (300 MHz, CDCl3) δ 7.38 (d, J=8.43 Hz, 1H), 6.49 (d, J=12.75 Hz, 1H), 5.73-5.56 (m, 2H), 3.76-3.61 (m, 2H), 2.14-1.43 (m, 16H), 1.08 (s, 3H), 0.92-0.78 (m, 2H), 0.66-0.57 (m, 2H).

Workup

  1. customThe mixture was then quenched by addition of 1N hydrochloric acid
  2. extractionThe mixture was extracted with dichloromethane (3×10 mL)
  3. washwashed with brine (15 mL)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-fd3ea822e5184ba2950bc212e4afb3d1
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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