Acetonitrile → 3-(3-(Cycloheptylmethoxy)phenyl)-3-hydroxypropanenitrile

HRID 74333Notes

Reaction equation

HRID 74333 reaction equation
[Li+].CC([N-]C(C)C)C.[C:9](#[N:11])[CH3:10].[CH:12]1([CH2:19][O:20][C:21]2[CH:22]=[C:23]([CH:26]=[CH:27][CH:28]=2)[CH:24]=[O:25])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1>CCCCCCC.C1COCC1.C(C1C=CC=CC=1)C.C1COCC1>[CH:12]1([CH2:19][O:20][C:21]2[CH:22]=[C:23]([CH:24]([OH:25])[CH2:10][C:9]#[N:11])[CH:26]=[CH:27][CH:28]=2)[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]1

Participants

6

Reactant 3

HCID 6342AcetonitrileHCID 2724682Lithium diisopropylamideHCID 866376133-(Cycloheptylmethoxy)benzaldehyde

Product 1

HCID 673170503-(3-(Cycloheptylmethoxy)phenyl)-3-hydroxypropanenitrile

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 22742125Tetrahydrofuran heptane ethylbenzolSolvent

Conditions

Temperature
0 °C

Procedure

To a −78° C. solution of LDA (10 mL of a 2M solution in heptane/THF/ethylbenzene, 20.09 mmol) in THF (30 mL) was added acetonitrile (0.97 mL, 18.41 mmol) dropwise over ca. 2 min. After stirring for 15 min, a solution of 3-(cycloheptylmethoxy)benzaldehyde (3.89 g, 16.74 mmol) in THF (20 mL) was added. The reaction was allowed to warm to 0° C. over 2 h then quenched with the addition of saturated aqueous NH4Cl (30 mL). The mixture was extracted with EtOAc twice. The combined organics were dried over Na2SO4 and concentrated under reduced pressure. Purification by flash chromatography (20% EtOAc-hexanes) gave 3-(3-(cycloheptylmethoxy)phenyl)-3-hydroxypropanenitrile as a colorless oil. Yield (2.102 g, 46%): 1H NMR (400 MHz, DMSO-d6) δ 7.22 (t, J=8.0 Hz, 1H), 6.95 (d, J=2.4 Hz, 1H), 6.93 (d, J=8.0 Hz, 1H), 6.81 (ddd, J=8.4, 2.4, 0.8 Hz, 1H), 5.89 (d, J=4.4 Hz, 1H), 4.83 (dt, J=6.4, 4.8 Hz, 1H), 3.71 (d, J=6.8 Hz, 2H), 2.86 (dd, J=16.8, 5.0 Hz, 1H), 2.78 (dd, J=16.4, 6.6 Hz, 1H), 1.86-1.92 (m, 1H), 1.76-1.82 (m, 2H), 1.61-1.67 (m, 2H), 1.37-1.59 (m, 6H), 1.20-1.30 (m, 2H).*

Workup

  1. customthen quenched with the addition of saturated aqueous NH4Cl (30 mL)
  2. extractionThe mixture was extracted with EtOAc twice
  3. dry with materialThe combined organics were dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customPurification by flash chromatography (20% EtOAc-hexanes)

Sources & evidence

ORD record
ord-7b571979e89243fa8824f9929cba5f16
Source dataset
uspto-grants-2014_09
Patent number
US08829244B2

Reaction notes

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