Sodium cyanoborohydride → HCID 178498770, compound

HRID 713873Notes

Reaction equation

HRID 713873 reaction equation
[C:1]([C@H:5]1[CH2:10][CH2:9][C@H:8]([O:11][C:12]2[C:13]([C:24]([F:27])([F:26])[F:25])=[C:14]3[C:19](=[CH:20][CH:21]=2)[CH:18]=[C:17]([CH:22]=O)[CH:16]=[CH:15]3)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[NH:28]1[CH2:31][CH:30]([C:32]([O:34][CH3:35])=[O:33])[CH2:29]1.[BH3-]C#N.[Na+]>C(O)C>[C:1]([C@H:5]1[CH2:10][CH2:9][C@H:8]([O:11][C:12]2[C:13]([C:24]([F:25])([F:26])[F:27])=[C:14]3[C:19](=[CH:20][CH:21]=2)[CH:18]=[C:17]([CH2:22][N:28]2[CH2:31][CH:30]([C:32]([O:34][CH3:35])=[O:33])[CH2:29]2)[CH:16]=[CH:15]3)[CH2:7][CH2:6]1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 5003444Sodium cyanoborohydrideHCID 20132751Methyl azetidine-3-carboxylateHCID 178445788HCID 178445788, compound

Product 1

HCID 178498770HCID 178498770, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

A mixture of 6-(trans-4-tert-butylcyclohexyloxy)-5-(trifluoromethyl)-2-naphthaldehyde (300 mg, 0.8 mmol) and methyl azetidine-3-carboxylate (184 mg, 1.6 mmol, 2.0 equiv) in anhydrous ethanol (20 mL) was refluxed for 2 h. Then the solvent was removed in vacuo, fresh ethanol and NaBH3CN (150 mg, 2.4 mmol, 3.0 equiv) was added, the resulting mixture was refluxed for 1 h. The reaction mixture was concentrated and the residue was purified by chromatography with silica gel (dichloromethane:methanol 20:1) to give product methyl 1-((6-(trans-4-tert-butylcyclohexyloxy)-5-(trifluoromethyl)naphthalen-2-yl)methyl)azetidine-3-carboxylate as a white solid (150 mg, yield: 40%), ESI-MS: 477.3 (M+H)+. HPLC: 85.67% 1H NMR (400 MHz, CD3OD) δ: 8.09 (dd, 1H), 8.01 (d, 1H), 7.56 (s, 1H), 7.46-7.51 (m, 2H), 4.42 (m, 1H), 3.77 (s, 2H), 3.71 (s, 3H), 3.57 (t, 2H), 3.45 (t, 2H), 3.35-3.39 (m, 1H), 2.18 (d, 2H), 1.88 (d, 2H), 1.43-1.52 (q, 2H), 1.09-1.22 (m, 3H), 0.89 (s, 9H).

Workup

  1. temperaturewas refluxed for 2 h
  2. additionwas added
  3. temperaturethe resulting mixture was refluxed for 1 h
  4. concentrationThe reaction mixture was concentrated
  5. customthe residue was purified by chromatography with silica gel (dichloromethane:methanol 20:1)

Sources & evidence

ORD record
ord-f69d69fccb494d94ad100e6128ad2638
Source dataset
uspto-grants-2015_11
Patent number
US09186367B2

Reaction notes

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