Sodium cyanoborohydride → {5-[3-(4-Trifluoromethyl-piperidin-1-yl)-propyl]-tricyclo [8.2.1.03,8]trideca-3(8),4,6-trien-13-yl}-carbamic Acid Tert-Butyl Ester

HRID 722146Notes

Reaction equation

HRID 722146 reaction equation
[C:1]([O:5][C:6](=[O:25])[NH:7][CH:8]1[CH:18]2[CH2:19][CH2:20][CH:9]1[CH2:10][C:11]1[CH:12]=[C:13]([CH2:21][CH2:22][CH:23]=O)[CH:14]=[CH:15][C:16]=1[CH2:17]2)([CH3:4])([CH3:3])[CH3:2].Cl.[F:27][C:28]([F:36])([F:35])[CH:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1.C([BH3-])#N.[Na+]>CO>[C:1]([O:5][C:6](=[O:25])[NH:7][CH:8]1[CH:18]2[CH2:19][CH2:20][CH:9]1[CH2:10][C:11]1[CH:12]=[C:13]([CH2:21][CH2:22][CH2:23][N:32]3[CH2:33][CH2:34][CH:29]([C:28]([F:36])([F:35])[F:27])[CH2:30][CH2:31]3)[CH:14]=[CH:15][C:16]=1[CH2:17]2)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 5003444Sodium cyanoborohydrideHCID 162181604-(Trifluoromethyl)piperidine hydrochlorideHCID 86591377[5-(3-Oxo-propyl)-tricyclo[8.2.1.03,8]trideca-3(8),4,6-trien-13-yl]-carbamic acid tert-butyl ester

Product 1

HCID 86591376{5-[3-(4-Trifluoromethyl-piperidin-1-yl)-propyl]-tricyclo [8.2.1.03,8]trideca-3(8),4,6-trien-13-yl}-carbamic Acid Tert-Butyl EsterYield 44.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The product from Step 2 (140 mg, 0.408 mmol), 4-trifluoromethylpiperidine hydrochloride (78 mg, 0.408 mmol) and sodium cyanoborohydride (77 mg, 1.22 mmol) in methanol (15 ml) were stirred at room temperature for 18 hours. The mixture was quenched with water and then with sodium bicarbonate solution (sat). The product was extracted with DCM and the organic phase was dried and concentrated. The crude product was purified by column chromatography on silica gel eluting with 40:1 DCM-2M NH3 in MeOH to give a colourless oil. The product was re-purified by column chromatography on silica gel eluting with 7:1 isohexane-ethyl acetate to give a colourless oil 87 mg (44%). 1H NMR (CDCl3, 400 MHz) δ 6.99 (1H, d, J=8.0 Hz), 6.89 (2H, m), 4.98 (1H, m), 4.02 (1H, m), 2.95–3.02 (4H, m), 2.45–2.62 (6H, m), 2.35 (2H, m), 1.58–2.04 (11H, m), 1.47 (9H, m), 1.19 (2H, m). m/z 481 (M+H+).

Workup

  1. customThe mixture was quenched with water
  2. extractionThe product was extracted with DCM
  3. customthe organic phase was dried
  4. concentrationconcentrated
  5. customThe crude product was purified by column chromatography on silica gel eluting with 40:1 DCM-2M NH3 in MeOH
  6. customto give a colourless oil
  7. customThe product was re-purified by column chromatography on silica gel eluting with 7:1 isohexane-ethyl acetate

Sources & evidence

ORD record
ord-20bf870e49f34d89b438c8ff24204b3b
Source dataset
uspto-grants-2006_11
Patent number
US07138400B2

Reaction notes

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