Methyl chloroformate → HCID 21035371, compound

HRID 1831989Notes

Reaction equation

HRID 1831989 reaction equation
FC(F)(F)C(O)=O.[NH2:8][CH2:9][C:10]1[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:11]=1[CH2:12][O:13][C:14]1[CH:19]=[C:18]([CH3:20])[N:17]([C:21]2[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=2[F:28])[C:16](=[O:29])[C:15]=1[Br:30].C(N(CC)CC)C.[CH3:43][O:44][C:45](Cl)=[O:46]>CC(N(C)C)=O>[Br:30][C:15]1[C:16](=[O:29])[N:17]([C:21]2[C:22]([F:28])=[CH:23][CH:24]=[CH:25][C:26]=2[F:27])[C:18]([CH3:20])=[CH:19][C:14]=1[O:13][CH2:12][C:11]1[CH:31]=[CH:32][C:33]([F:35])=[CH:34][C:10]=1[CH2:9][NH:8][C:45](=[O:46])[O:44][CH3:43]

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 22050385HCID 22050385, compound

Product 1

HCID 21035371HCID 21035371, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To solution of 4-{[2-(aminomethyl)-4-fluorobenzyl]oxy}-3-bromo-1-(2,6-difluorophenyl)-6-methylpyridin-2(1H)-one trifluoroacetate (0.12 g, 0.00021 mol) in dimethylacetamide (2.0 mL) at 0° C., was added triethylamine (0.06 mL, 0.00043 mol) followed by the addition of methylchloroformate (0.05 mL). The reaction mixture was stirred at room temperature for 30 min under argon atmosphere. Dimethylacetamide was distilled in vacuo and the residue was partitioned between dichloromethane (10 mL) and 5% citric acid (10 mL). The organic phase was washed with water, dried (Na2SO4) and concentrated to dryness. The resulting residue was purified by flash chromatography (60% EtOAc in hexane) to afford the title compound (0.09 g, 75%) as a white amorphous powder: 1H NMR (DMSO-d6/400 MHz) δ 7.68 (m, 1H), 7.62 (m, 1H), 7.59 (m, 1H) 7.38 (m, 2H), 7.115 (m, 2H), 6.78 (s, 1H), 5.38 (s, 2H), 4.31 (d, 2H, J=6.0 Hz), 3.53 (s, 3H), and 2.03 (s, 3H); 19F NMR (DMSO-d6/400 MHz) δ−113.77 (m), and −120.33 (m); ES-HRMS m/z 511.0508 (M+H C22H19N2O4F3Br requires 511.0475).

Workup

  1. distillationDimethylacetamide was distilled in vacuo
  2. customthe residue was partitioned between dichloromethane (10 mL) and 5% citric acid (10 mL)
  3. washThe organic phase was washed with water
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated to dryness
  6. customThe resulting residue was purified by flash chromatography (60% EtOAc in hexane)

Sources & evidence

ORD record
ord-0d9c39305402422b92eeeb7b01fd1ed6
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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