1,1,1-Trifluoro-2-propanol → (+/-)-5-(2,2,2-Trifluoro-1-methyl-ethoxy)-pyridine-2-carbonitrile

HRID 2041194Notes

Reaction equation

HRID 2041194 reaction equation
[F:1][C:2]([F:7])([F:6])[CH:3]([OH:5])[CH3:4].[H-].[Na+].Cl[C:11]1[CH:12]=[CH:13][C:14]([C:17]#[N:18])=[N:15][CH:16]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(P(N(C)C)(N(C)C)=O)C>[F:1][C:2]([F:7])([F:6])[CH:3]([CH3:4])[O:5][C:11]1[CH:12]=[CH:13][C:14]([C:17]#[N:18])=[N:15][CH:16]=1

Participants

6

Reactant 4

HCID 97741,1,1-Trifluoro-2-propanolHCID 10340Sodium CarbonateHCID 24758Sodium hydrideHCID 38339425-Chloro-2-cyanopyridine

Product 1

HCID 57656409(+/-)-5-(2,2,2-Trifluoro-1-methyl-ethoxy)-pyridine-2-carbonitrileYield 90.1%

Reagents, catalysts & solvents 1

HCID 12679HexamethylphosphoramideSolvent

Procedure

Add 1,1,1-trifluoro-2-propanol (971 mg, 8.5 mmol) slowly to a slurry of sodium hydride (205 mg, 60% mineral oil, washed with hexane) in HMPA (8 mL) under nitrogen at 0° C. Allow the slurry to warm to ambient temperature and stir for 5 min. Add 5-chloro-pyridine-2-carbonitrile (590 mg, 4.2 mmol), then heat the mixture at 90° C. for 4 h. Adjust the mixture to pH 9 with sodium carbonate then extract with diethyl ether (2×50 mL). Dry the combined organic extracts over Na2SO4 and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (95/5 to 80/20) to obtain the desired intermediate (818 mg, 89%). GC-MS m/z: 216 (M+).

Workup

  1. extractionthen extract with diethyl ether (2×50 mL)
  2. dry with materialDry the combined organic extracts over Na2SO4
  3. concentrationconcentrate in vacuo
  4. customPurify by chromatography on silica gel eluting with hexane/EtOAc (95/5 to 80/20)

Sources & evidence

ORD record
ord-6e9750dc753d47588022b687e856d877
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

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