3,4-Difluorophenol → 2-(3,4-Difluorophenoxy)-4-cyclohexyloxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine

HRID 750824Notes

Reaction equation

HRID 750824 reaction equation
CS([C:5]1[N:10]=[C:9]([O:11][CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]2)[C:8]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)=[C:7]([C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][C:26]=2[Cl:32])[N:6]=1)(=O)=O.C([Li])CCC.[F:38][C:39]1[CH:40]=[C:41]([OH:46])[CH:42]=[CH:43][C:44]=1[F:45]>>[F:38][C:39]1[CH:40]=[C:41]([CH:42]=[CH:43][C:44]=1[F:45])[O:46][C:5]1[N:10]=[C:9]([O:11][CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]2)[C:8]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)=[C:7]([C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][C:26]=2[Cl:32])[N:6]=1

Participants

4

Reactant 3

HCID 759273,4-DifluorophenolHCID 691979992-(Methylsulfonyl)-4-(cyclohexyloxy)-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidineHCID 178418339Butyllithium

Product 1

HCID 103255242-(3,4-Difluorophenoxy)-4-cyclohexyloxy-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidine

Procedure

2-(Methylsulfonyl)-4-(cyclohexyloxy)-5-(4-chlorophenyl)-6-(2,4-dichloro-phenyl)pyrimidine (Lower Rf product) (Example 52, Step A), (26 mg, 0.05 mmol) was reacted with 1 equivalent each of n-butyl lithium and 3,4-difluorophenol by the procedure described in Reference Examples 6 and 7. Workup and flash column chromatography on silica gel (eluted with 95/5 hexanes/ethyl acetate) afforded title compound. HPLC/MS: m/e=563 (M++1); Rt=5.25 min. 1H-NMR 500 MHz (CDCl3): 1.28-1.40 (m, 4H), 1.55 (m, 3H), 1.65 (m, 2H), 1.90 (m, 2H), 5.03 (m, J=4 Hz, 1H), 7.05 (m, 4H), 7.10 (m, 5H), 7.34 (d, J=2 Hz, 1H).

Sources & evidence

ORD record
ord-6f4e468e274746119d8d2934c53b19ca
Source dataset
uspto-grants-2008_07
Patent number
US07405221B2

Reaction notes

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