Potassium Carbonate → 2,4-Difluoro-6-methylamino-benzoic acid 2,2-dimethoxy-ethyl ester
Reaction equation
[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]([NH:12][CH3:13])[C:3]=1[C:4]([OH:6])=[O:5].C(=O)([O-])[O-].[K+].[K+].[CH3:20][O:21][CH:22]([O:25][CH3:26])[CH2:23]Br>CN(C=O)C>[CH3:20][O:21][CH:22]([O:25][CH3:26])[CH2:23][O:5][C:4](=[O:6])[C:3]1[C:7]([NH:12][CH3:13])=[CH:8][C:9]([F:11])=[CH:10][C:2]=1[F:1]Participants
Procedure
A mixture of example 12a (3.83 g, 20.5 mmol) and potassium carbonate (2.0 g, 14.4 mmol) in DMF (20 mL) was heated at 90° C. After stirring for 1 h, the mixture was cooled to r.t. Bromoacetaldehyde dimethyl acetal (3.74 g, 21.52 mmol) was added dropwise. After addition, the reaction mixture was heated to 130° C. for 11 h. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was dissolved in diethyl ether and passed through a silica plug, and concentrated under reduced pressure to yield 3.64 g (65%) of clean desired product as an orange oil. 1H NMR (400 MHz, DMSO-d6): δ 7.52 (bs, 1H), 6.31-6.46 (m, 2H), 4.66 (t, 1H, J=5.2 Hz), 4.23 (d, 2H, J=5.2 Hz), 3.34 (s, 6H), 2.81 (d, 3H, J=4.8 Hz). MS (ES) [m+H] calc'd for C12H15F2NO4, 276; found 276.
Workup
- additionAfter addition
- temperaturethe reaction mixture was heated to 130° C. for 11 h
- temperatureThe reaction mixture was cooled to room temperature
- concentrationconcentrated under reduced pressure
- dissolutionThe residue was dissolved in diethyl ether
- concentrationconcentrated under reduced pressure
Sources & evidence
- ORD record
- ord-afff7976d05d4c1f9bf543e357e92d31
- Source dataset
- uspto-grants-2011_11
- Patent number
- US08063066B2
Reaction notes
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