Acetone Cyanohydrin → HCID 68966024, compound

HRID 2116408Notes

Reaction equation

HRID 2116408 reaction equation
[Cl:1][C:2]1[CH:12]=[CH:11][C:5]2[CH2:6]C(CO)[O:8][C:4]=2[C:3]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[Cl:19].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.O[C:52]([CH3:56])([CH3:55])[C:53]#[N:54]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:12]=[CH:11][C:5]2[CH2:6][CH:55]([CH:52]([CH3:56])[C:53]#[N:54])[O:8][C:4]=2[C:3]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[Cl:19]

Participants

6

Reactant 4

HCID 6406Acetone CyanohydrinHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 68966173HCID 68966173, compound

Product 1

HCID 68966024HCID 68966024, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of (±)-[6-chloro-7-(2-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanol (0.5 g, 1.69 mmol) in toluene (10 mL) was added triphenylphosphine (0.66 g, 2.54 mmol), diethyl azodicarboxylate (0.44 g, 2.54 mmol), and 2-hydroxy-2-methylpropanenitrile (0.21 g, 2.53 mmol) and the reaction mixture was allowed to stir at room temperature for 48 h. The solvent was removed in vacuo to provide a crude oil. Purification by flash column chromatography (silica, ethyl acetate:hexanes 1:9-3:7) provided 0.22 g (43%) of (±)-{2-[6-chloro-7-(2-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]propanenitrile. To a solution of the nitrile in tetrahydrofuran (10 mL) was added borane-tetrahydrofuran (8 mL) and the reaction mixture was heated to reflux for 3 h. The reaction mixture was quenched with 1.0 N aqueous hydrogen chloride (100 mL) and then neutralized with 1.0 N aqueous sodium hydroxide (100 mL). The aqueous layer was extracted with ethyl acetate (2×200 mL) and the combined organic extracts were washed with saturated aqueous sodium chloride (100 mL), dried (magnesium sulfate) and the solvent removed in vacuo. Purification by flash column chromatography (silica, 10% ammonium hydroxide in methanol:dichloromethane 1:9) provided 0.1 g (19%) of (±)-{2-[6-chloro-7-(2-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]ethyl}amine as a white solid, hydrochloride salt. mp 211-213° C.

Workup

  1. customThe solvent was removed in vacuo
  2. customto provide a crude oil
  3. customPurification by flash column chromatography (silica, ethyl acetate:hexanes 1:9-3:7)

Sources & evidence

ORD record
ord-3d6c8ac8f9d64375a0d90d603e937e70
Source dataset
uspto-grants-2008_10
Patent number
US07435837B2

Reaction notes

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