Potassium Carbonate → HCID 22049896, compound
Reaction equation
[OH:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]([C:9]2[O:13][C:12]([C:14]([O:16][CH3:17])=[O:15])=[CH:11][CH:10]=2)[C:4](=[O:18])[CH:3]=1.[Br:19]N1C(=O)CCC1=O.C([O-])([O-])=O.[K+].[K+].[F:33][C:34]1[CH:41]=[C:40]([F:42])[CH:39]=[CH:38][C:35]=1[CH2:36]Br>CN(C=O)C>[Br:19][C:3]1[C:4](=[O:18])[N:5]([C:9]2[O:13][C:12]([C:14]([O:16][CH3:17])=[O:15])=[CH:11][CH:10]=2)[C:6]([CH3:8])=[CH:7][C:2]=1[O:1][CH2:36][C:35]1[CH:38]=[CH:39][C:40]([F:42])=[CH:41][C:34]=1[F:33]Participants
Procedure
To a room temperature solution of methyl 5-(4-hydroxy-6-methyl-2-oxopyridin-1(2H)-yl)-2-furoate (step 1) (3.19 g, 12.8 mmol) in DMF (14 mL) was added portion-wise solid N-bromosuccinimide (2.29 g, 12.9 mmol). The reaction was stirred vigorously for 1.0 h, followed by the sequential addition of K2CO3 (1.88 g, 13.6 mmol), DMF (4.0 mL), and 2,4 difluorobenzyl bromide (2.00 mL, 15.55 mmol). The resulting suspension was stirred for 9.0 hours until complete formation of desired product was seen by LCMS analysis. The reaction was then diluted with saturated brine (300 mL) and extracted with ethyl acetate (3×300 mL). The resulting organic extracts were Na2SO4 dried, filtered, and concentrated in vacuo to a residue that was subjected to SiO2 chromatography with a gradient elution using ethyl acetate/hexanes (40:60 to 60:40) to furnish a solid (3.20 mg, 55%). 1H NMR (400 MHz, d7-DMF) δ 7.78 (app q, J=8.6 Hz, 1H), 7.48 (app d, J=3.6 Hz, 1H), 7.33 (app dt, J=10.0, 2.4 Hz, 1H), 7.21 (app dt, J=8.5, 1.8 Hz, 1H), 6.92 (d, J=3.6 Hz, 1H), 6.81 (s, 1H), 5.47 (s, 2H), 3.88 (s, 3H), 2.15 (s, 3H); LC/MS C-18 column, tr=3.11 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50° C.). ES-MS m/z 454 (M+H). ES-HRMS m/z 454.0117 (M+H calcd for C19H15BrF2N2O5 requires 454.0096).
Sources & evidence
- ORD record
- ord-2edb076b79e848dd86cc1ce0e0e13c76
- Source dataset
- uspto-grants-2009_12
- Patent number
- US07629363B2
Reaction notes
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