Water → 7-(3,5-Difluorobenzyloxy)-3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-4,5,6,7-tetrahydrobenzo[d]isoxazole

HRID 509459Notes

Reaction equation

HRID 509459 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:15]2[C:19]3[CH2:20][CH2:21][CH2:22][CH:23]([OH:24])[C:18]=3[O:17][N:16]=2)[CH:6]=[CH:7][C:8]=1[N:9]1[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10]1.[H-].[Na+].Br[CH2:28][C:29]1[CH:34]=[C:33]([F:35])[CH:32]=[C:31]([F:36])[CH:30]=1.O>CN(C=O)C.C(OCC)(=O)C>[F:35][C:33]1[CH:34]=[C:29]([CH:30]=[C:31]([F:36])[CH:32]=1)[CH2:28][O:24][CH:23]1[C:18]2[O:17][N:16]=[C:15]([C:5]3[CH:6]=[CH:7][C:8]([N:9]4[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10]4)=[C:3]([O:2][CH3:1])[CH:4]=3)[C:19]=2[CH2:20][CH2:21][CH2:22]1

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 5188963,5-Difluorobenzyl bromideHCID 89545187HCID 89545187, compound

Product 1

HCID 715576567-(3,5-Difluorobenzyloxy)-3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-4,5,6,7-tetrahydrobenzo[d]isoxazole

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To the 3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-4,5,6,7-tetrahydrobenzo[d]isoxazol-7-ol (48 mg, 0.15 mmol) in DMF (2 ml) at 0° C., was added NaH (7 mg, 0.18 mmol). The mixture was stirred for 10 min before addition of 1-(bromomethyl)-3,5-difluorobenzene. Stirring was continued for 1 hr before addition of water (3 mL) and extraction with ethyl acetate. The organic phase was washed with water, brine, dried over MgSO4 and concentrated. The crude product was purified by preparative TLC using 5% of MeOH in DCM as solvent to afford the title product. 1H NMR (CDCl3) δ: 7.82 (br. s., 1H), 7.53 (s, 1H), 7.30-7.40 (m, 214), 6.89-7.03 (m, 2H), 6.73 (t, J=9.0 Hz, 1H), 4.84 (d, J=12.9 Hz, 1H), 4.76 (d, J=13.7 Hz, 1H), 4.64 (t, J 3.7 Hz, 1H), 3.93 (s, 3H), 2.73-2.82 (m, 1H), 2.57-2.68 (m, 1H), 2.33 (br. s., 314), 2.17-2.26 (m, 1H), 1.87-2.07 (m, 3H). MS(M+H)+=452.

Workup

  1. washThe organic phase was washed with water, brine
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. customThe crude product was purified by preparative TLC

Sources & evidence

ORD record
ord-738c2e3d33584beebde9a21f5343e63f
Source dataset
uspto-grants-2015_08
Patent number
US09096582B2

Reaction notes

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