Benzyl Alcohol → 2-(Benzyloxy)-5-chloro-3-fluoropyridine

HRID 237274Notes

Reaction equation

HRID 237274 reaction equation
[H-].[Na+].[CH2:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[Cl:11][C:12]1[CH:13]=[C:14]([F:19])[C:15](F)=[N:16][CH:17]=1.O>C1COCC1.CCOC(C)=O>[CH2:3]([O:10][C:15]1[C:14]([F:19])=[CH:13][C:12]([Cl:11])=[CH:17][N:16]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

7

Reactant 4

HCID 244Benzyl AlcoholHCID 962WaterHCID 24758Sodium hydrideHCID 27832485-Chloro-2,3-difluoropyridine

Product 1

HCID 673497402-(Benzyloxy)-5-chloro-3-fluoropyridineYield 67.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To 60% NaH in mineral oil (1.0 g, 25.0 mmol) in THF (25 mL) was added benzyl alcohol (2.7 g, 2.6 mL, 25.0 mmol) dropwise. After 1 h, 5-chloro-2,3-difluoro-pyridine (3.73 g, 25.0 mmol) was added in THF (5 mL). After an additional 18 h, H2O was added and the mixture extracted with EtOAc (2×). The combined organics were washed with brine and dried. Silica gel chromatography (1-15% EtOAc in hexanes) gave 4.02 g (67% yield) of the title compound as a clear oil. 1H NMR (CDCl3): 7.91 (d, J=2.2 Hz, 1H), 7.48-7.46 (m, 2H), 7.39-7.32 (m, 4H), 5.44 (s, 2H).

Workup

  1. waitAfter an additional 18 h
  2. extractionthe mixture extracted with EtOAc (2×)
  3. washThe combined organics were washed with brine
  4. customdried

Sources & evidence

ORD record
ord-c89d1fbd3e884cb28ead45e124a6174c
Source dataset
uspto-grants-2014_02
Patent number
US08642583B2

Reaction notes

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