Ethanol → HCID 11547594, compound

HRID 1178847Notes

Reaction equation

HRID 1178847 reaction equation
[F:1][C:2]([F:29])([F:28])[C:3]1[CH:4]=[C:5]([CH:21]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:23]=1)[CH2:6][O:7][CH2:8][C:9]1([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:13][CH2:12][C:11](=O)[CH2:10]1.[NH:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1.C(O)C.[BH4-].[Na+]>C1COCC1.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[F:1][C:2]([F:29])([F:28])[C:3]1[CH:4]=[C:5]([CH:21]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:23]=1)[CH2:6][O:7][CH2:8][C:9]1([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:13][CH2:12][CH:11]([N:30]2[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]2)[CH2:10]1

Participants

7

Reactant 4

HCID 702EthanolHCID 8082PiperidineHCID 4311764Sodium borohydrideHCID 58592526HCID 58592526, compound

Product 1

HCID 11547594HCID 11547594, compound

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 3-((3,5-bis(trifluoromethyl)benzyloxy)methyl)-3-phenylcyclopentanone (5 mg) in THF (0.10 mL) at room temperature was added piperidine (50 μL) followed by titanium(IV) isopropoxide and the resulting solution was heated at 65° C. in a sealed vial for 2 h. The solution was cooled to room temperature, 100 μL ethanol was added followed by sodium borohydride (4 mg), and the resulting suspension was stirred at room temperature for 1 h. The reaction mixture was then passed through a clean-up extraction column (2 g) and washed with methanol (0.3 mL). The filtrate was evaporated in vacuo, and the residue was purified by preparative TLC eluting with 10% MeOH/1% NH3.H2O/89% CH2Cl2 to give the title compound (1.2 mg). 1H NMR (400 MHz, CDCl3) δ 1.3-2.5 (m), 3.43 (d, J=8.8 Hz), 3.48 (d, J=8.8 Hz), 3.51 (d, J=8.0 Hz), 3.61 (d, J=8.0 Hz), 4.45 (s), 7.1-7.4 (m), 7.53 (s), 7.58 (s), 7.71 (s), and 7.74 (s). HPLC retention time (1.96 min, method A). MS: 486 (MH+).

Workup

  1. temperatureThe solution was cooled to room temperature
  2. extractionThe reaction mixture was then passed through a clean-up extraction column (2 g)
  3. washwashed with methanol (0.3 mL)
  4. customThe filtrate was evaporated in vacuo
  5. customthe residue was purified by preparative TLC
  6. washeluting with 10% MeOH/1% NH3.H2O/89% CH2Cl2

Sources & evidence

ORD record
ord-709b0950d9214d7bba0b8773f1d71840
Source dataset
uspto-grants-2007_10
Patent number
US07276631B2

Reaction notes

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