Water → HCID 22050127, compound

HRID 1866969Notes

Reaction equation

HRID 1866969 reaction equation
[OH:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]([C:9]2[C:10]([CH3:19])=[C:11]([CH:16]=[CH:17][CH:18]=2)[C:12]([O:14][CH3:15])=[O:13])[C:4](=[O:20])[CH:3]=1.[F:21][C:22]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:23]=1[CH2:24]Br.C([O-])([O-])=O.[K+].[K+].O>CN(C)C=O>[F:21][C:22]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:23]=1[CH2:24][O:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]([C:9]2[C:10]([CH3:19])=[C:11]([CH:16]=[CH:17][CH:18]=2)[C:12]([O:14][CH3:15])=[O:13])[C:4](=[O:20])[CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 902971-(Bromomethyl)-2,4-difluorobenzeneHCID 54724171HCID 54724171, compound

Product 1

HCID 22050127HCID 22050127, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Methyl-3-(4-hydroxy-6-methyl-2-oxopyridin-1(2H)-yl)-2-methylbenzoate (from Step 1) (42.0 g, 154 mmol) was stirred briskly at room temperature with 2,4-difluorobenzyl bromide (19.7 ml, 154 mmol) and K2CO3 (31.8 g, 231 mmol) in 250 ml of N,N-dimethylformamide. After stirring overnight, the reaction was poured into 1 L of cold water. The solution was extracted 3 times with ethyl acetate and the organic layers were dried over MgSO4, and evaporated. The product was carried on to the next step as a crude oil (60.4 g, 85%). 1H NMR (400 MHz, CDCl3) δ 7.96 (dd, J=7.85, 1.28 Hz, 1H), 7.45-7.34 (m, 2H), 7.27-7.23 (m, 1H), 6.94-6.84 (m, 2H), 5.98 (d, J=2.68 Hz, 1H), 5.92 (dd, J=2.69, 0.81 Hz, 1H), 5.01 (s, 2H), 3.88 (s, 3H), 2.28 (s, 3H), 1.81 (s, 3H); LC/MS, tr=2.96 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50° C.), ES-MS m/z 400 (M+H). ES-HRMS m/z 400.1341 (M+H calcd for C22H19F2NO4 requires 400.1355).

Workup

  1. extractionThe solution was extracted 3 times with ethyl acetate
  2. dry with materialthe organic layers were dried over MgSO4
  3. customevaporated
  4. customLC/MS, tr=2.96 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50° C.), ES-MS m/z 400 (M+H)

Sources & evidence

ORD record
ord-95bcee5a18f64347add4eb42121c8a63
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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