Water → HCID 86677877, compound

HRID 1499957Notes

Reaction equation

[C:1]([C:4]1[C:5]([O:18][CH2:19][CH3:20])=[C:6]([CH:12]2[CH2:16][NH:15][C:14](=[O:17])[CH2:13]2)[C:7](F)=[C:8]([Cl:10])[CH:9]=1)(=[O:3])[CH3:2].[C-:21]#[N:22].[Na+].O>CS(C)=O>[C:1]([C:4]1[CH:9]=[C:8]([Cl:10])[C:7]([C:21]#[N:22])=[C:6]([CH:12]2[CH2:13][C:14](=[O:17])[NH:15][CH2:16]2)[C:5]=1[O:18][CH2:19][CH3:20])(=[O:3])[CH3:2]

Participants

Conditions

Temperature: 80 °C

Procedure

A racemic mixture of 4-(3-acetyl-5-chloro-2-ethoxy-6-fluorophenyl)pyrrolidin-2-one (0.20 g, 0.67 mmol) (from Example 345, Step 5) and sodium cyanide (0.057 g, 1.2 mmol) in dimethyl sulfoxide (1.5 mL) was stirred at 80° C. for 3 h. The reaction mixture was poured into water (35 mL) and extracted with ethyl acetate (2×50 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated to give a crude residue. The crude material was purified by flash column chromatography using ether (containing 10% methanol) in hexanes (0%-100%) to give the desired product (0.15 g, 71%) as a mixture of enantiomers. LCMS for C15H16ClN2O3 (M+H)+: m/z=307.1; Found: 307.0. The mixture of enantiomers was separated by chiral HPLC to give the individual enantiomers as peak 1 and peak 2 (RT=5.00 min and 10.4 min; Phenomenex Lux Cellulose C-2, 21.2×250 mm, 5 micron particle size, eluting with 60% ethanol in hexanes at 18 mL/min).

Workup

extractionextracted with ethyl acetate (2×50 mL)
washThe combined organic extracts were washed with brine
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customto give a crude residue
customThe crude material was purified by flash column chromatography

Sources & evidence

ORD record: ord-e7208b93f7044e00a03dda2562595d27
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09199982B2

Reaction notes

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