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 475373Notes

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 (CT) 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-3204412f24f044d3bdd5d82e2037aa6e
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637546B2

Reaction notes

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