Borane;tetrahydrofuran → HCID 15941920, compound

HRID 2116409Notes

Reaction equation

HRID 2116409 reaction equation
[Cl:1][C:2]1[CH:14]=[CH:13][C:5]2[CH2:6][CH:7]([CH:9](C)[C:10]#[N:11])[O:8][C:4]=2[C:3]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[Cl:21].B.O1CCCC1>O1CCCC1>[Cl:1][C:2]1[CH:14]=[CH:13][C:5]2[CH2:6][CH:7]([CH2:9][CH2:10][NH2:11])[O:8][C:4]=2[C:3]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[Cl:21]

Participants

4

Reactant 2

HCID 2723981Borane;tetrahydrofuranHCID 68966024HCID 68966024, compound

Product 1

HCID 15941920HCID 15941920, compoundYield 19%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

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. temperaturethe reaction mixture was heated
  2. temperatureto reflux for 3 h
  3. customThe reaction mixture was quenched with 1.0 N aqueous hydrogen chloride (100 mL)
  4. extractionThe aqueous layer was extracted with ethyl acetate (2×200 mL)
  5. washthe combined organic extracts were washed with saturated aqueous sodium chloride (100 mL)
  6. dry with materialdried (magnesium sulfate)
  7. customthe solvent removed in vacuo
  8. customPurification by flash column chromatography (silica, 10% ammonium hydroxide in methanol:dichloromethane 1:9)

Sources & evidence

ORD record
ord-8275688028db4133966c90fb4fab2825
Source dataset
uspto-grants-2008_10
Patent number
US07435837B2

Reaction notes

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