Phenol → 4-(4-Methoxy-benzyloxy)-6-phenoxy-2-(4-trifluoromethyl-thiazol-2-yl)-pyrimidine

HRID 530744Notes

Reaction equation

HRID 530744 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)[N:5]=[C:4]([C:18]2[S:19][CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[N:22]=2)[N:3]=1.[C:27]1([OH:33])[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.[H-].[Na+]>CN(C=O)C>[CH3:17][O:16][C:13]1[CH:14]=[CH:15][C:10]([CH2:9][O:8][C:6]2[CH:7]=[C:2]([O:33][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[N:3]=[C:4]([C:18]3[S:19][CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[N:22]=3)[N:5]=2)=[CH:11][CH:12]=1

Participants

5

Reactant 3

HCID 996PhenolHCID 24758Sodium hydrideHCID 582826474-Chloro-6-(4-methoxy-benzyloxy)-2-(4-trifluoromethyl-thiazol-2-yl)pyrimidine

Product 1

HCID 582827464-(4-Methoxy-benzyloxy)-6-phenoxy-2-(4-trifluoromethyl-thiazol-2-yl)-pyrimidineYield 100%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred solution of compound 285 (246 mg, 1 eq.) in anhydrous DMF (5 mL) was added a solution of phenol (69 mg, 1.2 eq.) and NaH 60% in oil (29 mg, 1.2 eq.) in anhydrous DMF (5 mL). The resulting mixture was stirred at room temperature for 3 hrs and concentrated under reduced pressure. The crude material was solubilized in EtOAc (10 mL), and washed sequentially with water and brine. Organics were dried over MgSO4, filtered, and concentrated under reduced pressure to yield compound AH as a beige solid in 100% yield. 1H NMR (CDCl3, 400 MHz) δ 3.82 (s, 3H), 5.48 (s, 2H), 6.01 (s, 1H), 6.83-6.93 (m, 1H), 7.16-7.31 (m; 4H), 4.43 (m, 4H), 7.90 (s, 1H).

Workup

  1. concentrationconcentrated under reduced pressure
  2. washwashed sequentially with water and brine
  3. dry with materialOrganics were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto yield compound AH as a beige solid in 100% yield

Sources & evidence

ORD record
ord-7363a7acc1104305925e955e90331388
Source dataset
uspto-grants-2016_05
Patent number
US09353100B2

Reaction notes

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