Methanol → 3'-(((1-Methyl-4-(pyridin-4-yl)piperidin-4-yl)methoxy)methyl)-5'-(trifluoromethyl)biphenyl-4-carbonitrile

HRID 391483Notes

Reaction equation

HRID 391483 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]([CH2:19][O:20][CH2:21][C:22]3([C:35]4[CH:40]=[CH:39][N:38]=[CH:37][CH:36]=4)[CH2:27][CH2:26][N:25]([C:28](OC(C)(C)C)=O)[CH2:24][CH2:23]3)[CH:10]=2)=[CH:5][CH:4]=1)#[N:2].FC(F)(F)C(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CO>ClCCl>[CH3:28][N:25]1[CH2:26][CH2:27][C:22]([CH2:21][O:20][CH2:19][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:18])([F:16])[F:17])[CH:12]=2)([C:35]2[CH:36]=[CH:37][N:38]=[CH:39][CH:40]=2)[CH2:23][CH2:24]1

Participants

6

Reactant 4

HCID 887Methanol2×HCID 6422Trifluoroacetic acidHCID 5049666Sodium triacetoxyborohydrideHCID 58993558tert-Butyl 4-(((4'-cyano-5-(trifluoromethyl)biphenyl-3-yl)methoxy)methyl)-4-(pyridin-4-yl)piperidine-1-carboxylate

Product 1

HCID 589934633'-(((1-Methyl-4-(pyridin-4-yl)piperidin-4-yl)methoxy)methyl)-5'-(trifluoromethyl)biphenyl-4-carbonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A flask was charged with tert-butyl 4-(((4′-cyano-5-(trifluoromethyl)biphenyl-3-yl)methoxy)methyl)-4-(pyridin-4-yl)piperidine-1-carboxylate (50 mg, 0.091 mmol) and trifluoroacetic acid (1 mL, 13.0 mmol) in dichloromethane (5 mL) at 0° C. under nitrogen. After 20 min the solvent was evaporated under reduced pressure and the resulting residue dried overnight. The resulting oil was dissolved in dichloromethane (5 mL) and treated with formaldehyde (37 wt. % solution in water, 1.0 mL) at 0° C. After 20 min, the reaction was treated with sodium triacetoxyborohydride (77 mg, 0.363 mmol). 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 residue purified via preparative HPLC. The solvent was evaporated to afford 21 mg (50%). Mass Spec: 466.10 (MH)+. LC tr=2.325 min (Phenomenex-Luna 4.6×50 mm S10, 10% MeOH/90% H2O/0.1% TFA→90% MeOH/10% H2O/0.1% TFA Gradient Time=4 min, Flow rate=4 mL/min).

Workup

  1. customAfter 20 min the solvent was evaporated under reduced pressure
  2. customthe resulting residue dried overnight
  3. dissolutionThe resulting oil was dissolved in dichloromethane (5 mL)
  4. additiontreated with formaldehyde (37 wt. % solution in water, 1.0 mL) at 0° C
  5. customThe solvent was removed in vacuo
  6. customthe resulting residue purified via preparative HPLC
  7. customThe solvent was evaporated
  8. customto afford 21 mg (50%)

Sources & evidence

ORD record
ord-01dd425e715a4ed0912b037994d318cd
Source dataset
uspto-grants-2013_02
Patent number
US08383821B2

Reaction notes

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