Tributylphosphine → 4-(4-{3-[(2S)-2-methylpyrrolidinyl]propoxy}phenyl)-tetrahydro-2H-pyran-4-carbonitrile

HRID 272944Notes

Reaction equation

HRID 272944 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:14]#[N:15])[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C(P(CCCC)CCCC)CCC.[CH3:29][C@@H:30]1[CH2:34][CH2:33][CH2:32][N:31]1[CH2:35][CH2:36][CH2:37]O>C1(C)C=CC=CC=1.O1CCCC1>[NH3:15].[CH3:29][C@H:30]1[CH2:34][CH2:33][CH2:32][N:31]1[CH2:35][CH2:36][CH2:37][O:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:14]#[N:15])[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 13831TributylphosphineHCID 230916094-(4-Hydroxy-phenyl)-tetrahydro-pyran-4-carbonitrileHCID 574575603-[(2R)-2-Methylpyrrolidin-1-yl]propan-1-ol

Product 2

HCID 222AmmoniaHCID 685762634-(4-{3-[(2S)-2-methylpyrrolidinyl]propoxy}phenyl)-tetrahydro-2H-pyran-4-carbonitrileYield 42.6%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
85 °C

Procedure

A solution of 4-(4-hydroxy-phenyl)-tetrahydro-pyran-4-carbonitrile (203 mg, 1.0 mmol) and tri-n-butylphosphine (299 μL, 1.20 mmol) in toluene (6 mL) were added to a solution of 3-[(2R)-2-methylpyrrolidin-1-yl]propan-1-ol (172 mg, 1.20 mmol) in toluene (6 mL) and tetrahydrofuran (2 mL) at ambient temperature. 1′1-azobis(N,N-dimethylformamide) (206 mg, 1.20 mmol) was added and the reaction heated to 85° C. overnight. The reaction mixture was concentrated in vacuo followed by addition on dichloromethane (30 mL). The organic solution was then washed with NaOH (2.0M, 2×20 mL), dried with Na2SO4 and concentrated in vacuo. The compound was purified by column chromatography on Biotage® silica gel, eluting with dichloromethane:methanol:ammonia, 98:2:0.2 to 96:4:0.4 to give the title compound as a pale yellow oil (70 mg, 21%). HRMS (ESI+) 329.2224 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additionfollowed by addition on dichloromethane (30 mL)
  3. washThe organic solution was then washed with NaOH (2.0M, 2×20 mL)
  4. dry with materialdried with Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe compound was purified by column chromatography on Biotage® silica gel
  7. washeluting with dichloromethane

Sources & evidence

ORD record
ord-df08120a8f844f02b8881f0a6db5b54f
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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