Sodium Bromide → 1-[3-(5-Bromo-2-methoxy-benzyl)-azetidin-1-yl]-2,2,2-trifluoro-ethanone

HRID 237300Notes

Reaction equation

HRID 237300 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]([N:5]1[CH2:8][CH:7]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[O:16][CH3:17])[CH2:6]1)=[O:4].[Na+].[Br-:21].OOS([O-])=O.[K+].S(S([O-])=O)([O-])(=O)=O.[Na+].[Na+]>CC(C)=O.O.CCOC(C)=O>[Br:21][C:14]1[CH:13]=[CH:12][C:11]([O:16][CH3:17])=[C:10]([CH:15]=1)[CH2:9][CH:7]1[CH2:6][N:5]([C:3](=[O:4])[C:2]([F:1])([F:18])[F:19])[CH2:8]1

Participants

8

Reactant 4

HCID 253881Sodium BromideHCID 656671Sodium PyrosulfiteHCID 23707502Potassium hydroxy sulfiteHCID 584050552,2,2-Trifluoro-1-[3-(2-methoxy-benzyl)-azetidin-1-yl]-ethanone

Product 1

HCID 584051591-[3-(5-Bromo-2-methoxy-benzyl)-azetidin-1-yl]-2,2,2-trifluoro-ethanoneYield 53.5%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2,2,2-trifluoro-1-[3-(2-methoxy-benzyl)-azetidin-1-yl]-ethanone (95 mg, 0.35 mmol) in acetone (2 mL) and water (2 mL) was added NaBr (143 mg, 1.40 mmol) followed by Oxone (210 mg, 0.35 mmol). After 5 h, 10% sodium metabisulfite solution was added. After 1 h, EtOAc was added and the aqueous portion extracted twice with EtOAc. The combined organics were dried (Na2SO4) and concentrated. The crude product was purified by RP HPLC (basic conditions) to provide the title compound (66 mg, 53%). MS (ESI): mass calcd. for C13H13BrF3NO2, 352.1; m/z found, 354.1 [M+H]+. 1H NMR (CDCl3): 7.32 (dd, J=8.7, 2.5 Hz, 1H), 7.17 (d, J=2.5 Hz, 1H), 6.75 (t, J=10.2 Hz, 1H), 4.43 (dd, J=9.6, 8.4 Hz, 1H), 4.26-4.14 (m, 1H), 4.09 (dd, J=9.6, 5.7 Hz, 1H), 3.89 (dd, J=10.7, 5.7 Hz, 1H), 3.81 (s, 3H), 3.14-2.96 (m, 1H), 2.90 (d, J=7.8 Hz, 2H).

Workup

  1. waitAfter 1 h
  2. extractionthe aqueous portion extracted twice with EtOAc
  3. dry with materialThe combined organics were dried (Na2SO4)
  4. concentrationconcentrated
  5. customThe crude product was purified by RP HPLC (basic conditions)

Sources & evidence

ORD record
ord-9564c82bd14a4847bbd25b435b2711fa
Source dataset
uspto-grants-2014_02
Patent number
US08642583B2

Reaction notes

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