1-(Bromomethyl)-2,4-difluorobenzene → HCID 178490654, compound

HRID 1028166Notes

Reaction equation

HRID 1028166 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:23][CH3:24])=[C:6]([CH:22]=1)[C:7]([NH:9][C:10]1[S:11][C:12]2[C:17]([CH3:19])([CH3:18])[O:16][C:15]([CH3:21])([CH3:20])[C:13]=2[N:14]=1)=[O:8].CC(C)([O-])C.[K+].Br[CH2:32][C:33]1[CH:38]=[CH:37][C:36]([F:39])=[CH:35][C:34]=1[F:40]>CN(C)C=O.O1CCCC1.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:23][CH3:24])=[C:6]([CH:22]=1)[C:7](/[N:9]=[C:10]1\[S:11][C:12]2[C:17]([CH3:18])([CH3:19])[O:16][C:15]([CH3:20])([CH3:21])[C:13]=2[N:14]\1[CH2:32][C:33]1[CH:38]=[CH:37][C:36]([F:39])=[CH:35][C:34]=1[F:40])=[O:8]

Participants

6

Reactant 3

HCID 902971-(Bromomethyl)-2,4-difluorobenzeneHCID 23665647Potassium tert-butoxideHCID 87518926HCID 87518926, compound

Product 1

HCID 178490654HCID 178490654, compoundYield 5.1%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of Example 2A (0.3 g, 0.8 mmol) in N,N-dimethylformamide/tetrahydrofuran (1:4, 10 mL) were added potassium t-butoxide (0.11 g, 1.0 mmol) and 1-(bromomethyl)-2,4-difluorobenzene (Aldrich) (0.21 g, 1.0 mmol). The reaction was stirred at 80° C. overnight and then diluted with ethyl acetate (10 mL). The mixture was washed with 1M NaHCO3 and this aqueous layer was extracted with ethyl acetate (2×20 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated. The residue was purified by column chromatography using an Analogix® IT280™ (SiO2, 0-100% ethyl acetate in hexanes) to afford 20 mg (5%) of the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.47 (s, 6H) 1.52 (s, 6H) 3.72 (s, 3H) 5.35 (s, 2H) 7.07 (d, 3H) 7.32 (d, 1H) 7.37 (d, J=2.71 Hz, 1H) 7.40-7.50 (m, J=8.81 Hz, 1H); MS (ESI+) m/z 493 (M+H)+.

Workup

  1. washThe mixture was washed with 1M NaHCO3
  2. extractionthis aqueous layer was extracted with ethyl acetate (2×20 mL)
  3. dry with materialThe combined organic extracts were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-ddafb1c4260049298113a7347cfba405
Source dataset
uspto-grants-2014_05
Patent number
US08735434B2

Reaction notes

Loading…