Sodium Hydroxide → HCID 69023059, compound

HRID 860789Notes

Reaction equation

HRID 860789 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[O:9][N:10]=[C:11]3[CH:16]=[CH:15][C:14]([C:17]([C:25]4[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=4)([C:19]4[N:23]([CH3:24])[CH:22]=[N:21][CH:20]=4)O)=[CH:13][C:12]=23)[CH:5]=[CH:6][CH:7]=1.[OH-].[Na+]>O.C1COCC1>[NH2:10][C:11]1[CH:16]=[CH:15][C:14]([CH:17]([C:25]2[CH:26]=[CH:27][C:28]([Cl:31])=[CH:29][CH:30]=2)[C:19]2[N:23]([CH3:24])[CH:22]=[N:21][CH:20]=2)=[CH:13][C:12]=1[CH:8]([C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=1)[OH:9]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 22714354HCID 22714354, compound

Product 1

HCID 69023059HCID 69023059, compoundYield 21%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

TiCl3 15% in water (35 ml) was added slowly to a mixture of (±)-3-(3-chlorophenyl)-α-(4-chlorophenyl)-α-(1-methyl-1H-imidazol-5-yl)-2,1-benzisoxazole-5-methanol (prepared as described in WO 97/21701) (0.0111 mol) in THF (50 ml). The mixture was stirred at room temperature for 24 hours, basified with NaOH 3N, extracted with DCM, filtered over celite and pasted up with DCM. The organic layer was separated, dried (MgSO4), filtered and the solvent was evaporated till dryness. The residue (4.4 g) was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 96/4/0.1; 20–45 μm). Two pure fractions were collected and their solvents were evaporated, yielding 1.6 g F1 (34%) and 1 g of 2-amino-α-(3-chlorophenyl)-5-[(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-benzene methanol (21%). F1 was crystallized from acetonitrile and DIPE. The precipitate was filtered off, washed with diethyl ether and dried, yielding 0.8 g (16.5%) of [2-amino-5-[(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]phenyl](3-chlorophenyl)-methanone (intermediate 16), mp. 179° C.

Workup

  1. extractionextracted with DCM
  2. filtrationfiltered over celite
  3. customThe organic layer was separated
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe solvent was evaporated till dryness
  7. customThe residue (4.4 g) was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 96/4/0.1; 20–45 μm)
  8. customTwo pure fractions were collected
  9. customtheir solvents were evaporated

Sources & evidence

ORD record
ord-5a9a873ed5ed454890afb735710b9516
Source dataset
uspto-grants-2006_12
Patent number
US07153958B2

Reaction notes

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