Methanol → HCID 58993469, compound

HRID 391424Notes

Reaction equation

HRID 391424 reaction equation
Br[C:2]1[CH:3]=[C:4]([C@H:12]([O:14][CH2:15][C:16]2([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]2)[CH3:13])[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[C:35]([C:37]1[CH:42]=[CH:41][C:40](B(O)O)=[CH:39][CH:38]=1)#[N:36].CO>O1CCCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:35]([C:37]1[CH:42]=[CH:41][C:40]([C:2]2[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([C@H:12]([O:14][CH2:15][C:16]3([C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH2:17][CH2:18][N:19]([C:22]([O:24][C:25]([CH3:27])([CH3:28])[CH3:26])=[O:23])[CH2:20][CH2:21]3)[CH3:13])[CH:3]=2)=[CH:39][CH:38]=1)#[N:36]

Participants

6

Reactant 3

HCID 887Methanol2×HCID 27343264-Cyanophenylboronic acidHCID 58993483HCID 58993483, compound

Product 1

HCID 58993469HCID 58993469, compound

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
120 °C

Procedure

(R)-tert-Butyl 4-((1-(3-bromo-5-(trifluoromethyl)phenyl)ethoxy)methyl)-4-phenylpiperidine-1-carboxylate (0.35 g, 0.65 mmol), 4-cyanophenylboronic acid (284 mg, 1.93 mmol), and tetrakis(triphenylphosphine) palladium(0) (75 mg, 0.07 mmol) were combined in dry tetrahydrofuran (5 mL) in a microwave tube and sealed. After flushing with nitrogen, 2.3 mL of a 1 N potassium hydroxide aqueous solution was introduced. The mixture was heated at 120° C. for 1 h via microwave. After cooling to room temperature, the reaction mixture was concentrated and purified by flash chromatography on silica gel (15% ethyl acetate/hexanes) to afford 300 mg (82%) as an oil. LC/MS: tR=3.51 min, 565.23 (MH)+. (Phenomenex C18 4.6×50 mm, 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. customsealed
  2. customAfter flushing with nitrogen, 2.3 mL of a 1 N potassium hydroxide aqueous solution
  3. additionwas introduced
  4. temperatureAfter cooling to room temperature
  5. concentrationthe reaction mixture was concentrated
  6. custompurified by flash chromatography on silica gel (15% ethyl acetate/hexanes)
  7. customto afford 300 mg (82%) as an oil

Sources & evidence

ORD record
ord-4dc0e643f5ac4357914a80ffb0f3f8f2
Source dataset
uspto-grants-2013_02
Patent number
US08383821B2

Reaction notes

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