Water → 1-Chloroethyl 3-(2-(6-bromopyridin-2-yl)-2-methylhydrazono)-8-azabicyclo[3.2.1]octane-8-carboxylate

HRID 469691Notes

Reaction equation

HRID 469691 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N:8]([CH3:10])[NH2:9])[N:3]=1.O=[C:12]1[CH2:18][CH:17]2[N:19]([C:20]([O:22][CH:23]([Cl:25])[CH3:24])=[O:21])[CH:14]([CH2:15][CH2:16]2)[CH2:13]1.C1(C)C=CC(S(O)(=O)=O)=CC=1.O>C1(C)C=CC=CC=1>[Br:1][C:2]1[N:3]=[C:4]([N:8]([CH3:10])[N:9]=[C:12]2[CH2:13][CH:14]3[N:19]([C:20]([O:22][CH:23]([Cl:25])[CH3:24])=[O:21])[CH:17]([CH2:16][CH2:15]3)[CH2:18]2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6101p-Toluenesulfonic acidHCID 575147632-Bromo-6-(1-methylhydrazinyl)pyridineHCID 580922111-Chloroethyl 3-oxo-8-azabicyclo[3.2.1]octane-8-carboxylate

Product 1

HCID 580922041-Chloroethyl 3-(2-(6-bromopyridin-2-yl)-2-methylhydrazono)-8-azabicyclo[3.2.1]octane-8-carboxylateYield 28%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of 2-bromo-6-(1-methylhydrazinyl)pyridine (1.60 g, 7.90 mmol), 1-chloroethyl 3-oxo-8-azabicyclo[3.2.1]octane-8-carboxylate (1.80 g, 7.90 mmol) and p-toluenesulphonic acid (300 mg, 1.60 mmol) in toluene (50 mL) was heated under reflux, with water removal (azeotrope), for 3 h. The mixture was cooled to room temperature and concentrated. The residue was purified by flash column chromatography (silica gel, 0%-100% solvent mixture B in methylene chloride; solvent mixture B=80:18:2 methylene chloride/methanol/concentrated ammonium hydroxide) to give the title compound (676 mg, 28%) as a yellow solid: 1H NMR (500 MHz, CDCl3) δ 7.31 (t, J=7.5 Hz, 1H), 6.88 (d, J=7.5 Hz, 1H), 6.68-6.65 (m, 1H), 6.62 (d, J=8.0 Hz, 1H), 4.63-4.40 (m, 3H), 3.17 (s, 3H), 2.93-2.90 (m, 1H), 265-2.62 (m, 1H), 2.42-2.37 (dd, J=16.0, 6.0 Hz, 1H), 2.13-2.00 (m, 3H), 1.85 (d, J=6.0 Hz, 3H), 1.80-1.73 (m, 1H).

Workup

  1. concentrationconcentrated
  2. customThe residue was purified by flash column chromatography (silica gel, 0%-100% solvent mixture B in methylene chloride; solvent mixture B=80:18:2 methylene chloride/methanol/concentrated ammonium hydroxide)

Sources & evidence

ORD record
ord-667604bd4bc4485f81da2d8bb65b30a7
Source dataset
uspto-grants-2014_01
Patent number
US08629158B2

Reaction notes

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