Sodium cyanoborohydride → HCID 58993506, compound

HRID 391480Notes

Reaction equation

HRID 391480 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[C:11]([C@H:19]([O:21][CH2:22][C:23]3([C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)[CH2:28][CH2:27][N:26]([C:29](OC(C)(C)C)=O)[CH2:25][CH2:24]3)[CH3:20])[CH:10]=2)=[CH:5][CH:4]=1)#[N:2].FC(F)(F)C(O)=O.C(Cl)Cl.C([BH3-])#N.[Na+]>C(O)(=O)C>[CH3:29][N:26]1[CH2:25][CH2:24][C:23]([CH2:22][O:21][C@@H:19]([C:11]2[CH:10]=[C:9]([C:6]3[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][CH:5]=3)[CH:14]=[C:13]([C:15]([F:16])([F:17])[F:18])[CH:12]=2)[CH3:20])([C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)[CH2:28][CH2:27]1

Participants

5

Reactant 3

HCID 5003444Sodium cyanoborohydrideHCID 21863450Trifluoroacetic acid methylene chlorideHCID 58993469HCID 58993469, compound

Product 1

HCID 58993506HCID 58993506, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidCatalyst

Conditions

Temperature
0 °C

Procedure

(R)-tert-Butyl 4-((1-(4′-cyano-5-(trifluoromethyl)biphenyl-3-yl)ethoxy)methyl)-4-phenylpiperidine-1-carboxylate (300 mg, 0.53 mmol) was treated with a trifluoroacetic acid/methylene chloride mixture (1:1, 6 mL) for 1 h. The solvent was removed in vacuo and the resulting crude product dissolved in acetonitrile (5 mL), cooled to 0° C. and treated with formaldehyde (37 wt. % solution in water, 1.1 mL). The reaction was treated with sodium cyanoborohydride (163 mg, 2.58 mmol) and a few drops of acetic acid. The reaction was stirred at 0° C. for 30 min and at room temperature for 1 h. The solvent was removed in vacuo and the resulting crude mixture passed through a strong cation exchange column. After washing the column with several volumes of methanol, the product was eluted by washing the column with 2 M ammonia in methanol. The solvents were evaporated to afford 222 mg (73%). 1H-NMR (CDCl3, 300 MHz) δ 7.71 (s, 1H), 7.68 (s, 1H), 7.62 (s, 1H), 7.53 (s, 1H), 7.51 (s, 1H), 7.21-7.35 (m, 6H), 7.09-7.14 (m, 1H), 4.27 (q, J=6.6 Hz, 1H), 3.29 (d, J=9.2 Hz, 1H), 3.24 (d, J=8.8 Hz, 1H), 2.50-2.57 (m, 2H), 2.15 (s, 3H), 1.93-2.22 (m, 6H), 1.32 (m, 3H); 13C-NMR (CDCl3, 76 MHz) δ 146.5, 149.8, 140.0, 132.6, 131.4 (d, J=32.2 Hz), 128.0, 127.8, 127.7, 125.9, 123.8 (q, J=272.4 Hz), 122.8, 122.7, 122.0, 118.5, 111.6, 51.8, 50.2, 46.1, 40.1, 32.3, 31.9, 23.9. Mass spec.: 479.19 (MH)+.

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe resulting crude product dissolved in acetonitrile (5 mL)
  3. additiontreated with formaldehyde (37 wt. % solution in water, 1.1 mL)
  4. customThe solvent was removed in vacuo
  5. washAfter washing the column with several volumes of methanol
  6. washthe product was eluted
  7. washby washing the column with 2 M ammonia in methanol
  8. customThe solvents were evaporated
  9. customto afford 222 mg (73%)

Sources & evidence

ORD record
ord-843cae827e704211b82a65aba4c2df22
Source dataset
uspto-grants-2013_02
Patent number
US08383821B2

Reaction notes

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