Chlorosuccinimide → 3-[3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]-4-methylbenzoic acid

HRID 1832080Notes

Reaction equation

HRID 1832080 reaction equation
[F:1][C:2]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:3]=1[CH2:4][O:5][C:6]1[CH:11]=[C:10]([CH3:12])[N:9]([C:13]2[CH:14]=[C:15]([CH:19]=[CH:20][C:21]=2[CH3:22])[C:16]([OH:18])=[O:17])[C:8](=[O:23])[CH:7]=1.C1C(=O)N([Cl:36])C(=O)C1>ClC(Cl)C(O)=O.ClC(Cl)C>[Cl:36][C:7]1[C:8](=[O:23])[N:9]([C:13]2[CH:14]=[C:15]([CH:19]=[CH:20][C:21]=2[CH3:22])[C:16]([OH:18])=[O:17])[C:10]([CH3:12])=[CH:11][C:6]=1[O:5][CH2:4][C:3]1[CH:24]=[CH:25][C:26]([F:28])=[CH:27][C:2]=1[F:1]

Participants

5

Reactant 2

HCID 31398ChlorosuccinimideHCID 220503253-[4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]-4-methylbenzoic Acid

Product 1

HCID 220510673-[3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]-4-methylbenzoic acidYield 52%

Reagents, catalysts & solvents 2

HCID 6597Dichloroacetic AcidCatalystHCID 63651,1-DichloroethaneSolvent

Procedure

3-[4-[(2,4-Difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]-4-methylbenzoic acid (from above) (7.5 g, 19.4 mmol) and NCS (2.6 g, 19.4 mmol) were taken up in 65° C. dichloroethane (100 ml). A catalytic amount of dichloroacetic acid (2 drops) was added. After two hours the solvent was removed in vacuo and the residue was taken up in diethyl ether. The precipitate was collected on a filter pad and then taken up in 50% ethyl acetate/hexanes to remove residual succinimide. The precipitate was collected on a filter pad and then dried in vacuo to produce a white powder (4.2 g, 52%). 1H NMR (300 MHz, CD3OD) δ 8.10 (dd, J=7.85 1.81 Hz, 1H), 7.83 (d, J=8.26, 1.81 Hz, 1H), 7.40 (app q, J=8.26 Hz, 1H), 7.58 (d, J=7.85 Hz, 1H), 7.13-7.06 (m, 2H), 6.74 (s, 1H), 5.40 (s, 2H), 2.14 (s, 3H), 2.04 (s, 3H); ES-MS m/z 420 (M+H). ES-HRMS m/z 420.0786 (M+H calcd for C21H17ClF2NO4 requires 420.0809).

Workup

  1. customwere taken up in 65° C.
  2. customAfter two hours the solvent was removed in vacuo
  3. customThe precipitate was collected on a filter pad
  4. customto remove residual succinimide
  5. customThe precipitate was collected on a filter pad
  6. customdried in vacuo

Sources & evidence

ORD record
ord-364229657eff43c69947ce6e0ca2a2ad
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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