Thionyl Chloride → 3-Benzo[1,3]dioxol-5-ylpiperidin-1-yl-(R)-2,3-dihydrobenzo[1,4]dioxin-2-ylmethanone
Reaction equation
[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][C@@H:2]1[C:11]([OH:13])=O.S(Cl)(Cl)=O.Cl.[O:19]1[C:23]2[CH:24]=[CH:25][C:26]([CH:28]3[CH2:33][CH2:32][CH2:31][NH:30][CH2:29]3)=[CH:27][C:22]=2[O:21][CH2:20]1.CCN(C(C)C)C(C)C>C(Cl)Cl.O.C1(C)C=CC=CC=1>[O:19]1[C:23]2[CH:24]=[CH:25][C:26]([CH:28]3[CH2:33][CH2:32][CH2:31][N:30]([C:11]([C@@H:2]4[O:1][C:6]5[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=5[O:4][CH2:3]4)=[O:13])[CH2:29]3)=[CH:27][C:22]=2[O:21][CH2:20]1Participants
8
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 95 °C
Procedure
A mixture of (R)-2,3-dihydrobenzo[1,4]dioxine-2-carboxylic acid (167 mg, 0.93 mmol), thionyl chloride (338 μl, 551 mg, 4.63 mmol) and dry toluene was heated at 95° C. for 1.5 h and then evaporated to dryness. Toluene was added and the evaporation was repeated. The evaporation residue was dissolved in DCM (2 ml) and added slowly to a cold solution (0° C.) of 3-benzo[1,3]dioxol-5-yl-piperidine HCl (224 mg, 0.93 mmol) and DIPEA (0.324 ml, 240 mg, 1.85 mmol) in DCM (5 ml). The reaction mixture was stirred for 1 h 45 min at RT. Water was added, layers were separated and the organic phase was washed twice with 1 M HCl and sat. NaHCO3. The organic phase was dried (Na2SO4), filtered and evaporated to give 290 mg of the title compound.
Workup
- customevaporated to dryness
- additionToluene was added
- customthe evaporation
- dissolutionThe evaporation residue was dissolved in DCM (2 ml)
- customlayers were separated
- washthe organic phase was washed twice with 1 M HCl and sat. NaHCO3
- dry with materialThe organic phase was dried (Na2SO4)
- filtrationfiltered
- customevaporated
Sources & evidence
- ORD record
- ord-1335d4f8ec1f4b57b1c95abcea570aed
- Source dataset
- uspto-grants-2013_07
- Patent number
- US08492549B2
Reaction notes
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