Ethyl Acetate → 1-(4-(3-Cyanopropyl)-3-fluorobenzyl)cyclobutanecarbonitrile

HRID 1192878Notes

Reaction equation

HRID 1192878 reaction equation
N[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][C:11]#[N:12])=[C:4]([F:13])[CH:3]=1.[C:14]1(=O)[CH2:17][CH2:16][CH2:15]1.C[Si]([C:23]#[N:24])(C)C.[C:25](OCC)(=O)C>>[C:11]([CH2:10][CH2:9][CH2:8][C:5]1[CH:6]=[CH:7][C:2]([CH2:25][C:14]2([C:23]#[N:24])[CH2:17][CH2:16][CH2:15]2)=[CH:3][C:4]=1[F:13])#[N:12]

Participants

5

Reactant 4

HCID 8857Ethyl AcetateHCID 14496CyclobutanoneHCID 82115Trimethylsilyl cyanideHCID 576726094-(4-Amino-2-fluorophenyl)butanenitrile

Product 1

HCID 687319411-(4-(3-Cyanopropyl)-3-fluorobenzyl)cyclobutanecarbonitrileYield 92%

Conditions

Temperature
80 °C

Procedure

A mixture of 4-(4-Amino-2-fluorophenyl)butanenitrile (71) (30 mg, 0.17 mmol), cyclobutanone (24 mg, 0.34 mmol) and trimethylsilyl cyanide (TMSCN, 33 mg, 0.34 mmol) was heated to 80° C. and stirred for 15 h. To the medium was added ethyl acetate (2×20 mL) and then washed with water (2×20 mL). The organic layer was dried over MgSO4 and concentrated and the residue was purified with silica gel column chromatography (dichloromethane:acetone, 9:1) to give 1-(4-(3-Cyanopropyl)-3-fluorobenzyl)cyclobutanecarbonitrile (70) (40 mg, 92%): 1H NMR δ 7.01 (dd, 1H, J=8.0, 7.5 Hz), 6.37 (dd, 1H, J=8.0, 2.4 Hz), 6.34 (dd, 1H, J=11.8, 2.4 Hz), 4.18 (br s, 1H), 2.76-2.81 (m, 2H), 2.70 (t, 2H, J=7.3 Hz), 2.33-2.39 (m, 2H), 2.33 (t, 2H, J=7.1 Hz) 2.12-2.30 (m, 2H), 1.90-1.95 (m, 2H).

Workup

  1. washwashed with water (2×20 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated
  4. customthe residue was purified with silica gel column chromatography (dichloromethane:acetone, 9:1)

Sources & evidence

ORD record
ord-18c4b0ec99d14c1bb27afea888ce686c
Source dataset
uspto-grants-2014_03
Patent number
US08680291B2

Reaction notes

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