Benzyl (4-methylpiperidin-4-yl)carbamate → 4-benzyloxycarbonylamino-4methyl-3,4,5,6-tetrahydro-2H-(1,2')bipyridinyl-5'-carboxylic acid tert-butyl ester

HRID 1642691Notes

Reaction equation

[CH2:1]([O:8][C:9](=[O:18])[NH:10][C:11]1([CH3:17])[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:19]([O:23][C:24](=[O:32])[C:25]1[CH:30]=[CH:29][C:28](F)=[N:27][CH:26]=1)([CH3:22])([CH3:21])[CH3:20]>O1CCOCC1>[C:19]([O:23][C:24]([C:25]1[CH:30]=[CH:29][C:28]([N:14]2[CH2:15][CH2:16][C:11]([NH:10][C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[O:18])([CH3:17])[CH2:12][CH2:13]2)=[N:27][CH:26]=1)=[O:32])([CH3:22])([CH3:20])[CH3:21]

Participants

Conditions

Temperature: 80 °C

Procedure

To a stirred solution of (4-methyl-piperidin-4-yl)-carbamic acid benzyl ester (0.31 g, 1.28 mmol, Example 30B) in dioxane (5.0 mL) at room temperature was added 6-fluoro-nicotinic acid tert-butyl ester (0.21 g, 1.07 mmol). The reaction mixture was stirred at 80° C. for 18 hours, concentrated under reduced pressure and purified by flash chromatography with 10% to 30% ethyl acetate in hexane to provide 4-benzyloxycarbonylamino-4-methyl-3,4,5,6-tetrahydro-2H-(1,2′)bipyridinyl-5′-carboxylic acid tert-butyl ester. MS (CI) m/z 426 (M+1)+; 1H NMR (300 MHz, CDCl3) δ ppm 8.74 (d, 1H), 7.97 (dd, 1H), 7.35 (m, 5H), 7.26 (s, 1H), 5.07 (s, 2H), 4.68 (s, 1H), 3.97 (m, 2H), 3.37 (m, 2H), 2.08 (m, 2H), 1.66 (m, 2H), 1.56 (s, 9H), 1.42 (s, 3H).

Workup

concentrationconcentrated under reduced pressure
custompurified by flash chromatography with 10% to 30% ethyl acetate in hexane

Sources & evidence

ORD record: ord-58dcb002479042fe95bd8f3957e7e0cd
Source dataset: uspto-grants-2012_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08119664B2

Reaction notes

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