Sodium Hydroxide → HCID 178523763, compound

HRID 2391002Notes

Reaction equation

HRID 2391002 reaction equation
[Cl:1][C:2]1[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][C:3]=1[C:4]([NH:6][C@H:7]1[CH2:12][CH2:11][C@H:10]([CH:13]=O)[CH2:9][CH2:8]1)=[O:5].[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]2[C:31]([NH2:35])=[N:32][O:33][CH:34]=2)=[CH:26][CH:25]=1.[BH4-].[Na+].[OH-].[Na+]>[Cl-].[Na+].O.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].CO.C(OCC)(=O)C>[Cl:1][C:2]1[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][C:3]=1[C:4]([NH:6][C@H:7]1[CH2:12][CH2:11][C@H:10]([CH2:13][NH:35][C:31]2[C:30]([C:27]3[CH:28]=[CH:29][C:24]([Cl:23])=[CH:25][CH:26]=3)=[CH:34][O:33][N:32]=2)[CH2:9][CH2:8]1)=[O:5]

Participants

9

Reactant 4

HCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 574658984-(4-Chlorophenyl)isoxazol-3-amineHCID 178520978HCID 178520978, compound

Product 1

HCID 178523763HCID 178523763, compound

Reagents, catalysts & solvents 4

HCID 11026Titanium isopropoxideCatalystHCID 887MethanolSolvent2×HCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A mixture of trans-2-chloro-N-(4-formyl-cyclohexyl)-5-trifluoromethyl-benzamide (Example 1 Step 3) (100 mg, 0.30 mmol) and 4-(4-chlorophenyl)isoxazol-3-amine (this compound can be prepared according to method described in ‘Chemistry of Heterocyclic Compounds’ (New York, N.Y., United States) (2007), 43(1), 118-119) (58 mg, 0.300 mmol) is stirred in titanium(IV) isopropoxide (1 ml, 3.4 mmol) for 3 h. A thick slurry results. After 3 h, methanol (5 ml) is added followed by slow addition of sodium borohydride (18 mg, 0.5 mmol). after 5 minutes, sodium hydroxide solution 91 ml, 0.1M) is added to the reaction followed by dilution with ethyl acetate and brine. The organic extract is washed with brine, dried over MgSO4 and the solvent removed in vacuo. Purification by chromatography on silica, eluting with chloroform-ethanol (10:1) affords a sample of product containing minor amounts of starting materials. Trituation with methanol yields a pure sample or the title compound. MS m/z 512.3 [M+H]+; 1H NMR (400 MHz, CDCl3) δ 1.25 8H, m), 1.75 (1H, m), 1.95 (2H, m), 2.22 (2H, m), 3.20 (2H, d), 4.00 (1H, m), 5.97 (1H, d), 7.35 (2H, d), 7.45 (2H, d), 7.55 (1H, d), 7.62 (1H, d), 7.90 (1H, s), 8.15 (1H, s).

Workup

  1. customcan be prepared
  2. customA thick slurry results
  3. waitafter 5 minutes
  4. extractionThe organic extract
  5. washis washed with brine
  6. dry with materialdried over MgSO4
  7. customthe solvent removed in vacuo
  8. customPurification by chromatography on silica
  9. washeluting with chloroform-ethanol (10:1)
  10. customaffords a sample of product
  11. additioncontaining minor amounts of starting materials

Sources & evidence

ORD record
ord-8fadcc472f2348808a1b6e5b970bc108
Source dataset
uspto-grants-2012_09
Patent number
US08273900B2

Reaction notes

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