Cyclohexane → tert-butyl (2R)-2-ethynylpyrrolidine-1-carboxylate

HRID 2261896Notes

Reaction equation

Br[C:2](Br)=[CH:3][C@H:4]1[CH2:8][CH2:7][CH2:6][N:5]1[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10].C([Li])(CC)C.C1CCCCC1>C1COCC1>[C:3]([C@H:4]1[CH2:8][CH2:7][CH2:6][N:5]1[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])#[CH:2]

Participants

Conditions

Temperature: -78 °C

Procedure

Tert-butyl (2R)-2-(2,2-dibromovinyl)pyrrolidine-1-carboxylate (Intermediate XXXVIII, 8.1 g, 22.8 mmol) was dissolved in dry THF (200 mL) and cooled to −78° C. Then added sec-butyllithium 1.4M in cyclohexane (32.6 mL, 45.6 mmol) over 30 minutes and continued mixing an additional 30 minutes before quenching with 20% ammonium chloride solution (200 mL). The mixture was warmed to rt and diluted with ethyl ether (200 mL). The organic phase was separated, washed with brine, dried in vacuo and purified on a silica gel column using a 100% to 99:1 gradient of methylene chloride to methanol as mobile phase to yield pure tert-buty (2R)-2-ethynylpyrrolidine-1-carboxylate. LC-MS m/z (minus t-butyl+1)=220. 1H NMR (CD3OD, 400 Mhz) 4.44 ppm (s, 1H), 3.44-3.37 (m, 1H), 3.34-3.25 (m, 1H), 2.61 (s, 1H), 2.08-1.85 (m, 4H), 1.47 (s, 9H).

Workup

additioncontinued mixing an additional 30 minutes
custombefore quenching with 20% ammonium chloride solution (200 mL)
temperatureThe mixture was warmed to rt
additiondiluted with ethyl ether (200 mL)
customThe organic phase was separated
washwashed with brine
customdried in vacuo
custompurified on a silica gel column

Sources & evidence

ORD record: ord-6694fc2d4b944e029a74a6c59d16fae4
Source dataset: uspto-grants-2010_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07847100B2

Reaction notes

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