Trifluoroacetic acid → 3-Chloro-4-(2,4-difluorobenzyloxy)-1H-pyridin-2-one

HRID 1866972Notes

Reaction equation

HRID 1866972 reaction equation
[F:1][C:2]1[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:3]=1[CH2:4][O:5][C:6]1[CH:11]=[CH:10][NH:9][C:8](=[O:12])[CH:7]=1.[Cl:18]N1C(=O)CCC1=O.C(#N)C.O.FC(F)(F)C(O)=O>CN(C)C=O.C(OCC)C>[Cl:18][C:7]1[C:8](=[O:12])[NH:9][CH:10]=[CH:11][C:6]=1[O:5][CH2:4][C:3]1[CH:13]=[CH:14][C:15]([F:17])=[CH:16][C:2]=1[F:1]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 31398ChlorosuccinimideHCID 18373917Acetonitrile--water (1/1)HCID 220503904-(2,4-difluorobenzyloxy)-1H-pyridin-2-one

Product 1

HCID 220499783-Chloro-4-(2,4-difluorobenzyloxy)-1H-pyridin-2-one

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

4-[(2,4-difluorobenzyl)oxy]-pyridin-2(1H)-one (from Step 2) (8.60 g, 36.3 mmol) was stirred in 150 ml dimethylformamide and treated with N-chlorosuccinimide (5.4 g, 39.9 mmol). After 15 hours, the precipitate was collected by filtration (5.11 g, 52%) yielding a lustrous white solid. The mother liquor was diluted to 500 ml with diethyl ether, providing 2.47 g (25%) in a second crop. 1H-NMR (400 MHz, DMSO-d6) δ 11.87 (s, 1H), 7.60 (quartet, J=6.34 Hz, 1H), 7.43 (d, J=7.58 Hz, 1H), 7.31 (dt, J=10.08, 2.21 Hz, 1H), 7.14 (dt, J=8.65, 1.79 Hz, 1H), 6.44 (d, J=7.49 Hz, 1H), 5.28 (s, 1H). 19F-NMR (400 MHz, DMSO-d6) δ −109.58 (quintet, J=7.75 Hz, 1F), −113.68 (quartet, J=8.68 Hz, 1F). LC/MS tr=4.47 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes at 1 ml/min with detection at 254 nm, at 50° C.) ES-MS m/z 272, 274 3:1 (M+H).

Workup

  1. filtrationthe precipitate was collected by filtration (5.11 g, 52%)
  2. customyielding a lustrous white solid
  3. customproviding 2.47 g (25%) in a second crop

Sources & evidence

ORD record
ord-4923e9b67579457b9c0543c987d1ee98
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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