Toluene → 4-Chloro-2-(2-pyrrolidin-1-yl-ethoxy)benzonitrile

HRID 555710

Reaction equation

HRID 555710 reaction equation
[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4](F)[CH:3]=1.[N:11]1([CH2:16][CH2:17][OH:18])[CH2:15][CH2:14][CH2:13][CH2:12]1.C1(C)C=CC=CC=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+]>C1COCC1>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:18][CH2:17][CH2:16][N:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)[CH:3]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 762881-PyrrolidineethanolHCID 936554-Chloro-2-fluorobenzonitrileHCID 3251421Potassium bis(trimethylsilyl)amide

Product 1

HCID 630928984-Chloro-2-(2-pyrrolidin-1-yl-ethoxy)benzonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 4-chloro-2-fluoro-benzonitrile (869 mg, 5.58 mmol) and 2-pyrrolidin-1-yl-ethanol (0.80 mL, 6.70 mmol) in THF (30 mL) is treated with a 0.5 M toluene solution of KHMDS (13.4 mL, 6.7 mmol) at 0° C. After completion of the reaction at RT, the reaction mixture is quenched by H2O. EtOAc is added and the organic layer is washed with brine, dried over MgSO4. Concentration in vacuo affords the corresponding 4-chloro-2-(2-pyrrolidin-1-ylethoxy)-benzonitrile. A THF (7 mL) solution of 4-chloro-2-(2-pyrrolidin-1-yl-ethoxy)-benzonitrile is added to a suspension of LAH (293 mg, 7.71 mmol) in THF (50 mL) at 0° C. The reaction is allowed to stir for 2 h at ambient temperature and then quenched by Na2SO4.10H2O, and the product is isolated by filtration with Celite and washed with THF and dried under reduced pressure to give the title compound as oil; ES-MS: M+=255.2; HPLC: AtRet=1.22 min.

Workup

  1. customAfter completion of the reaction at RT
  2. customthe reaction mixture is quenched by H2O
  3. additionEtOAc is added
  4. washthe organic layer is washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationConcentration in vacuo

Sources & evidence

ORD record
ord-3b1205e84b074fd29d04851432cdc90a
Source dataset
uspto-grants-2011_11
Patent number
US08053457B2

Linked notes

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