Toluene → Tert-butyl-6-cyano-6-(pyridine-2-YL)-3-azabicyclo[3.1.0]hexane-3-carboxylate

HRID 455288Notes

Reaction equation

[C:1]([CH:3]1[CH:8]2[CH:4]1[CH2:5][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:7]2)#[N:2].F[C:17]1C=CC=C[N:18]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[C:33]1(C)C=C[CH:36]=[CH:35][CH:34]=1>>[C:12]([O:11][C:9]([N:6]1[CH2:5][CH:4]2[CH:8]([C:3]2([C:17]#[N:18])[C:1]2[CH:36]=[CH:35][CH:34]=[CH:33][N:2]=2)[CH2:7]1)=[O:10])([CH3:15])([CH3:14])[CH3:13]

Participants

Reactant 4

HCID 1140Toluene

HCID 97462-Fluoropyridine

HCID 3251421Potassium bis(trimethylsilyl)amide

HCID 59529950Tert-butyl 6-cyano-3-azabicyclo[3.1.0]hexane-3-carboxylate

Product 1

HCID 70219399Tert-butyl-6-cyano-6-(pyridine-2-YL)-3-azabicyclo[3.1.0]hexane-3-carboxylateYield 41%

Procedure

To a solution of 3 (700 mg, 3.36 mmol) in toluene (16 mL) at 0° C. was added 2-fluoropyridine (326 mg, 3.36 mmol) and a solution of KHMDS (0.5M in toluene, 6.72 mL, 3.36 mmol). The reaction was warmed to room temperature and stirred for 18 h. The crude reaction was purified by column chromatography using 0 to 60% EtOAc in hexanes to afford 10 (390 mg, 41%) as a clear oil; 1H-nmr (400 MHz, CDCl3) δ 8.46 (d, J=4.0 Hz, 1H), 7.75-7.66 (m, 2H), 7.17 (td, J=7.0, 1.5 Hz, 1H), 3.95 (d, J=12.5 Hz, 1H), 3.86 (d, J=12.5 Hz, 1H), 3.81-3.71 (m, 2H), 2.69 (s, 2H), 1.88 (d, J=5.0 Hz, 4H), 1.48 (s, 9H); LC-MS (214 nM) 2.96 min (>98%), m/z 286.1 [M+H].

Workup

customThe crude reaction
customwas purified by column chromatography

Sources & evidence

ORD record: ord-f7164558915d48798af602fa0c354e5a
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08497289B2

Reaction notes

Loading…