Methanol → HCID 86602718, compound

HRID 1178859Notes

Reaction equation

HRID 1178859 reaction equation
[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=1)[CH2:6][O:7][CH2:8][C:9]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:14][CH2:13][CH2:12][C:11](=O)[CH2:10]1.[CH3:31][OH:32].[BH4-].[Na+].[OH2:35].[CH3:36][NH2:37]>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[F:1][C:2]([F:30])([F:29])[C:31]([OH:35])=[O:32].[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=1)[CH2:6][O:7][CH2:8][C:9]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:14][CH2:13][CH2:12][CH:11]([NH:37][CH3:36])[CH2:10]1

Participants

7

Reactant 5

HCID 887MethanolHCID 962WaterHCID 6329MethylamineHCID 4311764Sodium borohydrideHCID 219731213-((3,5-Bis(trifluoromethyl)benzyloxy)methyl)-3-phenylcyclohexanone

Product 1

HCID 86602718HCID 86602718, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 11026Titanium isopropoxideCatalyst

Conditions

Temperature
80 °C

Procedure

To a solution of 3-((3,5-bis(trifluoromethyl)benzyloxy)methyl)-3-phenylcyclohexanone (10 mg) in methylamine (2.0 M solution in THF, 0.11 mL) at room temperature was added titanium(IV) isopropoxide (0.02 mL) and the resulting solution was heated at 80° C. in a sealed vial for 1.5 h. The solution was cooled to room temperature, 0.1 mL methanol was added followed by sodium borohydride (4.4 mg), and the resulting suspension was stirred at room temperature for 2 h. H2O was added to quench the reaction and the mixture was extracted with dichloromethane 3 times. The combined organic layers were concentrated and residue was purified by preparative HPLC to give the title compound (8 mg, 62% yield). 1H NMR (500 MHz, CD3OD) δ 1.39 (1H, m), 1.56 (1H, m), 1.72 (1H, m), 1.88 (1H, m), 2.14 (1H, m), 2.39 (1H, m), 2.61 (1H, m), 2.70 (3H, d, J=25 Hz), 2.71 (1H, m), 3.44 (1H, d, J=5 Hz), 3.79 (2H, dd, J=10, 60 Hz), 4.49-4.60 (2H, m), 7.21-7.28 (1H, m), 7.33 (1H, t, J=8 Hz), 7.38-7.46 (3H, m), 7.65 (1H, s), 7.72 (1H, s), 7.82 (1H, d, J=10 Hz). HPLC purity (retention time): 95% (2.05 min, method C). MS: 446.49 (MH+).

Workup

  1. temperatureThe solution was cooled to room temperature
  2. customto quench
  3. customthe reaction
  4. extractionthe mixture was extracted with dichloromethane 3 times
  5. concentrationThe combined organic layers were concentrated
  6. customresidue was purified by preparative HPLC

Sources & evidence

ORD record
ord-d32c2ab6716b4a8c990588e91b49b3fe
Source dataset
uspto-grants-2007_10
Patent number
US07276631B2

Reaction notes

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