Diisopropylethylamine → (4-methyl-5'-trifluoromethyl-3,4,5,6-tetrahydro-2H-(1,2')bipyridinyl-4-yl)-carbamic acid benzyl ester

HRID 1642679Notes

Reaction equation

Cl.[CH2:2]([O:9][C:10](=[O:19])[NH:11][C:12]1([CH3:18])[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl[C:21]1[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][N:22]=1.C(N(C(C)C)CC)(C)C>O1CCOCC1>[CH2:2]([O:9][C:10](=[O:19])[NH:11][C:12]1([CH3:18])[CH2:17][CH2:16][N:15]([C:21]2[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][N:22]=2)[CH2:14][CH2:13]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

Conditions

Temperature: 150 °C

Procedure

To a stirred solution of (4-methyl-piperidin-4-yl)-carbamic acid benzyl ester hydrochloride salt (0.15 g, 0.53 mmol, Example 30B) in dioxane (1.0 mL) at room temperature was added 2-chloro-5-trifluoromethyl-pyridine (0.11 g, 0.6 mmol) and diisopropylethyl amine (0.21 mL, 1.2 mmol). The reaction mixture was stirred at 150° C. in a microwave for 180 minutes, concentrated under reduced pressure and purified by flash chromatography with 30% ethyl acetate in hexane to provide (4-methyl-5′-trifluoromethyl-3,4,5,6-tetrahydro-2H-(1,2′)bipyridinyl-4-yl)-carbamic acid benzyl ester. MS (CI) m/z 394 (M+1)+; 1H NMR (300 MHz, CDCl3) δ ppm 8.38 (d, 1H), 7.61 (d,d 1H), 7.40-7.30 (m, 5H), 6.66 (d, 1H), 5.07 (s, 2H), 4.71-4.67 (m, 1H), 3.93 (m, 2H), 3.36 (m, 2H), 2.10 (m, 2H), 1.68 (m, 2H), 1.42 (s, 3H).

Workup

concentrationconcentrated under reduced pressure
custompurified by flash chromatography with 30% ethyl acetate in hexane

Sources & evidence

ORD record: ord-fca526c5994c4fed8d2edb66c2fed8be
Source dataset: uspto-grants-2012_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08119664B2

Reaction notes

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