Bromomethylcyclopropane → Tert-butyl 4-cyano-4-(cyclopropylmethyl)piperidine-1-carboxylate

HRID 1441234Notes

Reaction equation

C([N-]C(C)C)(C)C.[Li+].[C:9]([CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]1)#[N:10].Br[CH2:25][CH:26]1[CH2:28][CH2:27]1>C1COCC1.[Cl-].[Na+].O>[C:9]([C:11]1([CH2:25][CH:26]2[CH2:28][CH2:27]2)[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]1)#[N:10]

Participants

Conditions

Temperature: -70 °C

Procedure

To a stirred solution of lithium diisopropylamide (2M solution in THF; 60 ml; 0.12 mol) in THF (60 ml) at −70° C. was added tert-butyl 4-cyanopiperidine-1-carboxylate (21 g; 0.1 mol) in THF (150 ml) over 1 hour. The mixture was stirred at −70° C. for 1 hour and then (bromomethyl)cyclopropane (17.53 g; 0.13 mol) in THF (20 ml) was added. The solution was stirred at −70° C. for 1 hour then allowed to warm to ambient temperature over 2 hours. The reaction was poured into brine (150 ml) and extracted with EtOAc (3×200 ml). The combined organic extracts were washed with brine (200 ml), dried over MgSO4, filtered and evaporated to give a brown oil. The crude product was chromatographed on silica eluted with 5% EtOAc in isohexane to give the title product as a colourless oil. (24.8 g)

Workup

stirringThe solution was stirred at −70° C. for 1 hour
temperatureto warm to ambient temperature over 2 hours
extractionextracted with EtOAc (3×200 ml)
washThe combined organic extracts were washed with brine (200 ml)
dry with materialdried over MgSO4
filtrationfiltered
customevaporated
customto give a brown oil
customThe crude product was chromatographed on silica
washeluted with 5% EtOAc in isohexane

Sources & evidence

ORD record: ord-6fbb7f74cc6f4b4685783b53b9325fbd
Source dataset: uspto-grants-2010_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07655644B2

Reaction notes

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