Potassium hydride → HCID 68904417, compound

HRID 1869259Notes

Reaction equation

HRID 1869259 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH3:11].[H-].[K+].[C:14]1([C@H:20]2[O:22][C@@H:21]2[CH2:23][OH:24])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>ClCCl.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C@@H:20]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C@H:21]([OH:22])[CH2:23][OH:24])[CH:6]=[C:5]2[CH3:11]

Participants

6

Reactant 3

HCID 82127Potassium hydrideHCID 150502((2R,3R)-3-phenyloxiran-2-yl)methanolHCID 223515035-Fluoro-3-methyl-1H-indole

Product 1

HCID 68904417HCID 68904417, compound

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 5-fluoro-3-methyl-1H-indole (2.91 g, 19.5 mmol) and potassium hydride 50% dispersion in mineral oil (2.8 g, 35.1 mmol) in dichloromethane (40 mL) was stirred for 10 minutes under nitrogen at room temperature. A solution of [(2R,3R)-3-phenyloxiran-2-yl]methanol (2.0 g, 13.0 mmol) and titanium isopropoxide (4.3 mL, 14.3 mmol) in dichloromethane (10 mL) was then added and the mixture was stirred at room temperature for 12 hours. After disappearance of the epoxide, the mixture was partitioned between a 1N aqueous solution of hydrochloric acid (50 mL) and ethyl acetate (50 mL). The organic layer was separated, washed with saturated sodium bicarbonate (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified via Biotage chromatography (FlasH40i, silica, 60% ethyl acetate/hexane) to give (2S,3S)-3-(5-fluoro-3-methyl-1H-indol-1-yl)-3-phenylpropane-1,2-diol. MS (ESI) m/z 300

Workup

  1. stirringthe mixture was stirred at room temperature for 12 hours
  2. customAfter disappearance of the epoxide, the mixture was partitioned between a 1N aqueous solution of hydrochloric acid (50 mL) and ethyl acetate (50 mL)
  3. customThe organic layer was separated
  4. washwashed with saturated sodium bicarbonate (50 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified via Biotage chromatography (FlasH40i, silica, 60% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-d7205d248676470d950d4e1188bde1c7
Source dataset
uspto-grants-2009_12
Patent number
US07638512B2

Reaction notes

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