Methanol → 3-Pyrrolidinecarbonitrile, 4-(2,4-difluorophenyl)-, (4R)-

HRID 1361296Notes

Reaction equation

C([N:5]1[CH2:9][C@@H:8]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=2[F:17])[CH:7]([C:18]#[N:19])[CH2:6]1)(C)(C)C.ClC(OC(Cl)C)=O.CN(C)C1C2C(=CC=CC=2N(C)C)C=CC=1.CO>ClCCCl>[F:17][C:11]1[CH:12]=[C:13]([F:16])[CH:14]=[CH:15][C:10]=1[C@@H:8]1[CH2:9][NH:5][CH2:6][CH:7]1[C:18]#[N:19]

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of (4R)-1-t-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carbonitrile (4 g, 15.15 mmol) prepared according to the procedure described in WO 2004/09126 in DCE (10 ml) was added dropwise 1-chloroethyl chloroformate (2.45 ml, 22.68 mmol) at 0° C. The reaction solution was heated to 70° C., and maintaining this temperature, 1.8-bis(dimethylamino)naphthalene (4.87 g, 22.72 mmol) in DCE (10 ml) was added dropwise for 2 h. After the reaction finished, methanol (10 ml) was added, and maintaining the temperature, the reaction mixture was stirred for additional 1 h, concentrated in vacuo, and the next reaction was carried out without further purification.

Workup

additionwas added dropwise for 2 h
temperaturemaintaining the temperature
concentrationconcentrated in vacuo
customthe next reaction
customwas carried out without further purification

Sources & evidence

ORD record: ord-49f5e2e0a1264bf2bcfb27a960a75d55
Source dataset: uspto-grants-2011_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07879852B2

Reaction notes

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