Water → tert-Butyl 4-{[6-(1,2-dihydroxyethyl)-2-(trifluoromethyl)pyrimidin-4-yl]oxy}piperidine-1-carboxylate

HRID 1426354Notes

Reaction equation

HRID 1426354 reaction equation
[F:1][C:2]([F:26])([F:25])[C:3]1[N:8]=[C:7]([O:9][CH:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)[CH:6]=[C:5]([CH:23]=[CH2:24])[N:4]=1.CN1CC[O:31]CC1.[OH2:34]>CO.C(O)(C)(C)C.[Os](=O)(=O)(=O)=O>[OH:34][CH:23]([C:5]1[N:4]=[C:3]([C:2]([F:1])([F:25])[F:26])[N:8]=[C:7]([O:9][CH:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:21])([CH3:20])[CH3:22])=[O:17])[CH2:12][CH2:11]2)[CH:6]=1)[CH2:24][OH:31]

Participants

7

Reactant 3

HCID 962WaterHCID 79724-Methylmorpholine2×HCID 67954436tert-Butyl 4-{[2-(trifluoromethyl)-6-vinylpyrimidin-4-yl]oxy}piperidine-1-carboxylate

Product 1

HCID 69675751tert-Butyl 4-{[6-(1,2-dihydroxyethyl)-2-(trifluoromethyl)pyrimidin-4-yl]oxy}piperidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 30318Osmium TetroxideCatalystHCID 887MethanolSolventHCID 6386tert-ButanolSolvent

Procedure

To a solution of tert-butyl 4-{[2-(trifluoromethyl)-6-vinylpyrimidin-4-yl]oxy}piperidine-1-carboxylate (614 mg, 1.64 mmol) in methanol (7 mL) and tert-butyl alcohol (5.2 mL) was added TV-methylmorpholine TV-oxide (212 mg, 1.81 mmol) and water (5.2 mL). To this solution was then added osmium tetraoxide (20.9 mg, 0.0822 mmol). After stirring for 3 hours, another equivalent of TV-methylmorpholine TV-oxide was added. The reaction was stirred at room temperature overnight. The solution was concentrated and diluted with water and extracted with ethyl acetate twice, washed with brine, dried over Na2SO4, filtered and concentrated. The crude was purified by flash chromatography on a silica gel column to give the desired product. LCMS (M+H)+: 408.2.

Workup

  1. stirringThe reaction was stirred at room temperature overnight
  2. concentrationThe solution was concentrated
  3. additiondiluted with water
  4. extractionextracted with ethyl acetate twice
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude was purified by flash chromatography on a silica gel column

Sources & evidence

ORD record
ord-8e4ce8e9cb5a44e6a8c78655f1be227d
Source dataset
uspto-grants-2015_01
Patent number
US08933085B2

Reaction notes

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