Trifluoroacetic anhydride → (6-Chloro-5-(1-fluorocyclobutyl)pyridin-2-yl)methanol

HRID 624994Notes

Reaction equation

HRID 624994 reaction equation
FC(F)(F)C(OC(=O)C(F)(F)F)=[O:4].[Cl:14][C:15]1[C:20]([C:21]2([F:25])[CH2:24][CH2:23][CH2:22]2)=[CH:19][CH:18]=[C:17]([CH3:26])[N+:16]=1[O-].[OH-].[Na+]>ClCCl>[Cl:14][C:15]1[N:16]=[C:17]([CH2:26][OH:4])[CH:18]=[CH:19][C:20]=1[C:21]1([F:25])[CH2:24][CH2:23][CH2:22]1

Participants

5

Reactant 3

HCID 9845Trifluoroacetic anhydrideHCID 14798Sodium HydroxideHCID 902025652-Chloro-3-(1-fluorocyclobutyl)-6-methylpyridine 1-oxide

Product 1

HCID 90202593(6-Chloro-5-(1-fluorocyclobutyl)pyridin-2-yl)methanolYield 32.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic anhydride (1.27 g, 840 μL, 6.04 mmol) was added under ice cooling to a solution of 2-chloro-3-(1-fluorocyclobutyl)-6-methylpyridine 1-oxide (Example 130 c, 869 mg, 4.03 mmol) in dichloromethane (10.9 mL). The mixture was stirred at ambient temperature for 72 h. Upon ice bath cooling 5 N NaOH solution (1 mL) and afterwards ice water (20 mL) were added. The mixture was extracted with dichloromethane (2×40 mL). The combined organic layers were washed with icewater/brine (20 mL), dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, 50 g, heptane/EtOAc 0-40% in 120 min.) to give the title compound (279 mg, 32%) as light yellow oil, MS (ESI): m/e=216.3 [MH+].

Workup

  1. additionwere added
  2. extractionThe mixture was extracted with dichloromethane (2×40 mL)
  3. washThe combined organic layers were washed with icewater/brine (20 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography (silica gel, 50 g, heptane/EtOAc 0-40% in 120 min.)

Sources & evidence

ORD record
ord-7567c34d616342eb902b3812b38737bd
Source dataset
uspto-grants-2016_04
Patent number
US09303012B2

Reaction notes

Loading…