Dimethylformamide → 7-(5-Bromopyridin-2-yl)-7-azaspiro[3.5]nonan-2-ol

HRID 336535Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[CH:4][C:5](F)=[N:6][CH:7]=1.Cl.[CH2:10]1[C:13]2([CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)[CH2:12][CH:11]1[OH:19].C(N(CC)C(C)C)(C)C.CN(C=O)C>C(#N)C.C(OCC)(=O)C.O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:16]2[CH2:17][CH2:18][C:13]3([CH2:10][CH:11]([OH:19])[CH2:12]3)[CH2:14][CH2:15]2)=[N:6][CH:7]=1

Participants

Conditions

Temperature: 95 °C

Procedure

0.24 g (1.35 mmol) of 5-bromo-2-fluoropyridine, 0.20 g (1.13 mmol) of 7-azaspiro[3.5]nonan-2-ol hydrochloride (JP 2003246780) and 0.51 g (3.94 mmol) of N,N-diisopropylethylamine in 3 mL of acetonitrile are placed in a sealed tube. 1 mL of DMF is added and the mixture is then heated at 95° C. for 12 hours. The reaction mixture is allowed to cool to room temperature and is then taken up in ethyl acetate and water. The aqueous phase is separated out and the combined organic phases are then washed with saturated aqueous ammonium chloride solution and dried over sodium sulfate, and the filtrate is concentrated under reduced pressure. After purification by chromatography on silica gel, eluting with a 95/5/0.5 mixture of dichloromethane, methanol and 28% aqueous ammonia, 0.138 g pure product is thus obtained in the form of a colourless gum.

Workup

temperatureto cool to room temperature
customThe aqueous phase is separated out
washthe combined organic phases are then washed with saturated aqueous ammonium chloride solution
dry with materialdried over sodium sulfate
concentrationthe filtrate is concentrated under reduced pressure
customAfter purification by chromatography on silica gel
washeluting with a 95/5/0.5 mixture of dichloromethane, methanol and 28% aqueous ammonia, 0.138 g pure product
customis thus obtained in the form of a colourless gum

Sources & evidence

ORD record: ord-344938c8d485402a8ad6a85ab6408f08
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889702B2

Reaction notes

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