Potassium tert-butoxide → tert-Butyl 4-(((4'-cyano-5-(trifluoromethyl)biphenyl-3-yl)methoxy)methyl)-4-(pyridin-4-yl)piperidine-1-carboxylate

HRID 391459

Reaction equation

HRID 391459 reaction equation
Br[CH2:2][C:3]1[CH:4]=[C:5]([C:13]2[CH:18]=[CH:17][C:16]([C:19]#[N:20])=[CH:15][CH:14]=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[OH:21][CH2:22][C:23]1([C:36]2[CH:41]=[CH:40][N:39]=[CH:38][CH:37]=2)[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]1.CC(C)([O-])C.[K+]>O1CCCC1.C(=O)(O)[O-].[Na+]>[C:19]([C:16]1[CH:17]=[CH:18][C:13]([C:5]2[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=[C:3]([CH2:2][O:21][CH2:22][C:23]3([C:36]4[CH:37]=[CH:38][N:39]=[CH:40][CH:41]=4)[CH2:24][CH2:25][N:26]([C:29]([O:31][C:32]([CH3:34])([CH3:35])[CH3:33])=[O:30])[CH2:27][CH2:28]3)[CH:4]=2)=[CH:14][CH:15]=1)#[N:20]

Participants

6

Reactant 3

HCID 23665647Potassium tert-butoxide2×HCID 589934903'-(Bromomethyl)-5'-(trifluoromethyl)biphenyl-4-carbonitrileHCID 58993619tert-Butyl 4-(hydroxymethyl)-4-(pyridin-4-yl)piperidine-1-carboxylate

Product 1

HCID 58993558tert-Butyl 4-(((4'-cyano-5-(trifluoromethyl)biphenyl-3-yl)methoxy)methyl)-4-(pyridin-4-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
0 °C

Procedure

A flask was charged with 3′-(bromomethyl)-5′-(trifluoromethyl)biphenyl-4-carbonitrile (157 mg, 0.462 mmol) and tert-butyl 4-(hydroxymethyl)-4-(pyridin-4-yl)piperidine-1-carboxylate (90 mg, 0.308 mmol) in tetrahydrofuran (10 mL) at 0° C. The reaction was treated with potassium tert-butoxide (34.6 mg, 0.308 mmol), stirred at 0° C. for 20 min, and treated with another aliquot of potassium tert-butoxide (34.6 mg, 0.308 mmol). The reaction was allowed to warm to room temperature for 30 min, then diluted with 10% sodium bicarbonate, and extracted with ethyl acetate (2×). The organic layers were pooled together, washed with brine (1×), dried over sodium sulfate, and concentrated. Column chromatography on silica gel (0%→65% ethyl acetate/hexanes) gave 50 mg (29%). Mass spec.: 552.18 (MH)+ LC tr=2.54 min (HPLC Method 1).

Workup

  1. temperatureto warm to room temperature for 30 min
  2. extractionextracted with ethyl acetate (2×)
  3. washwashed with brine (1×)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customColumn chromatography on silica gel (0%→65% ethyl acetate/hexanes) gave 50 mg (29%)
  7. custom552.18 (MH)+ LC tr=2.54 min (HPLC Method 1)

Sources & evidence

ORD record
ord-9479dbe2eec84484bf351d53c5ff7a1b
Source dataset
uspto-grants-2013_02
Patent number
US08383821B2

Linked notes

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