S-Nicotine-5-carboxaldehyde → 3-Ethynyl-5-(1-methyl-2-pyrrolidinyl)pyridine

HRID 901307Notes

Reaction equation

[C:1](O[K])(C)(C)C.P(=O)(OC=[N+]=[N-])OC.[CH3:15][N:16]1[CH2:20][CH2:19][CH2:18][C@H:17]1[C:21]1[CH:22]=[C:23]([CH:27]=O)[CH:24]=[N:25][CH:26]=1>C1COCC1>[C:27]([C:23]1[CH:24]=[N:25][CH:26]=[C:21]([CH:17]2[CH2:18][CH2:19][CH2:20][N:16]2[CH3:15])[CH:22]=1)#[CH:1]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of tBuOK in THF (0.08 mL, 0.08 mmol) cooled at −78° C. was added dropwise a solution of methyl diazomethyl phosphonate in THF (0.1 mL, 0.08 mmol). The solution was stirred at −78° C. for 5 min, then a solution of 5-(1-methylpyrrolidin-2-yl)pyridine-3-carbaldehyde (V) (0.0126 g, 0.066 mmol) in THF (1 mL) was added via a double tipped needle. The reaction mixture was stirred at −78° C. for 16 h then allowed to warn to RT over 2 h. After evaporation of the solvent under reduced pressure, the crude material was purified by RPLC (silica gel, 10% EtOAC/hexanes) to afford 0.0061 g (51%) of 3-ethynyl-5-(1-methylpyrrolidin-2-yl)-pyridine (VI) as a clear oil. The data were identical to those described in the literature (Bleicher, L. S.; Cosford, N. P. D.; Herbault, A.; McCallum, J. S.; McDonald, I. A. J. Org. Chem. 1998, 63, 1109).

Workup

stirringThe reaction mixture was stirred at −78° C. for 16 h
waitto warn to RT over 2 h
customAfter evaporation of the solvent under reduced pressure
customthe crude material was purified by RPLC (silica gel, 10% EtOAC/hexanes)

Sources & evidence

ORD record: ord-9f1d5ec0a3614773b7bf47ce521f2f93
Source dataset: uspto-grants-2008_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07361768B2

Reaction notes

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