m-Chlorophenylacetonitrile → (4S)-2-(3-chlorophenyl)-4-hydroxy-6-[(phenylmethyl)oxy]hexanenitrile

HRID 2099293Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]#[N:10])[CH:5]=[CH:6][CH:7]=1.C([Li])CCC.[C:16]1([CH2:22][O:23][CH2:24][CH2:25][C@@H:26]2[CH2:28][O:27]2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]([CH2:28][C@H:26]([OH:27])[CH2:25][CH2:24][O:23][CH2:22][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:9]#[N:10])[CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: -78 °C

Procedure

(3-Chlorophenyl)acetonitrile (8.62 mL, 72.9 mmol) in 100 ml of THF was cooled to −78° C. Butyllithium (35.1 mL, 56.1 mmol, 1.6 M in THF) was added over 20 minutes and stirred for an additional 15 min at −78° C. (2R)-2-{2-[(phenylmethyl)oxy]ethyl}oxirane (10.0 g, 56.1 mmol, Synthesis 1992, 7, 621-623) in 20 mL of THF was added over 30 minutes and stirred for an additional hour at −78° C. After warming to room temperature the solvent was evaporated and the orange red oil was chromatographed on silica gel with 20-25% EtOAc in Hexanes to give the title compound (11.05 g, 58%). 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 1.8 (m, 3H) 3.6 (m, 1H) 3.7 (m, 2H) 4.1 (m, 2H) 4.5 (m, 2H) 7.3 (m, 9H).

Workup

additionwas added over 30 minutes
temperatureAfter warming to room temperature the solvent
customwas evaporated
customthe orange red oil was chromatographed on silica gel with 20-25% EtOAc in Hexanes

Sources & evidence

ORD record: ord-66afa5da8e76452dae12883c50c56b42
Source dataset: uspto-grants-2009_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07569579B2

Reaction notes

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