Trimethylamine oxide → HCID 57523124, compound

HRID 79012Notes

Reaction equation

HRID 79012 reaction equation
[C:1]([O:5][C:6](=[O:17])[C:7]1[CH:12]=[CH:11][C:10]([CH2:13]Br)=[C:9]([F:15])[C:8]=1[F:16])([CH3:4])([CH3:3])[CH3:2].C[N+]([O-:22])(C)C>CS(C)=O.C(Cl)Cl>[C:1]([O:5][C:6](=[O:17])[C:7]1[CH:12]=[CH:11][C:10]([CH:13]=[O:22])=[C:9]([F:15])[C:8]=1[F:16])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 1145Trimethylamine oxideHCID 575231234-Bromomethyl-2,3-difluoro-benzoic acid tert-butyl ester

Product 1

HCID 57523124HCID 57523124, compoundYield 43%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-bromomethyl-2,3-difluoro-benzoic acid tert-butyl ester (12.9 g, 42.1 mmol) in DMSO (80 mL) and DCM (40 mL) at 0° C. was added trimethylamine N-oxide (3.4 g, 45.3 mmol). The reaction mixture was stirred at room temperature for 18 hours before being concentrated in vacuo. The resultant residue was partitioned between iced water and ethyl acetate. The organic layer was separated and washed with brine twice, dried (Na2SO4), filtered and evaporated in vacuo. The resultant residue which was subjected to flash chromatography (Si—PPC, gradient 0% to 10%, TBME in cyclohexane) to afford the title compound as a white solid (4.34 g, 43%). 1H NMR (CDCl3, 400 MHz) 10.38 (1 H, d, J=0.8 Hz), 7.71 (1 H, dddd, J=7.4, 5.6, 1.7, 0.8 Hz), 7.63 (1 H, ddd, J=7.4, 5.6, 1.5 Hz), 1.61 (9 H, s).

Workup

  1. concentrationbefore being concentrated in vacuo
  2. customThe resultant residue was partitioned between iced water and ethyl acetate
  3. customThe organic layer was separated
  4. washwashed with brine twice
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated in vacuo

Sources & evidence

ORD record
ord-f482f6ab4fb04ba29c75ee76188c1099
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Reaction notes

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