Methanesulfonic Acid → 6-(4-Chloro-2,6-dimethoxyphenyl)piperidin-2-one

HRID 594370Notes

Reaction equation

HRID 594370 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[C:4]([O:10][CH3:11])[CH:3]=1.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.CS(O)(=O)=O.[O:31]=[C:32]1[NH:37][C@H:36](C(O)=O)[CH2:35][CH2:34][CH2:33]1>O>[Cl:1][C:2]1[CH:3]=[C:4]([O:10][CH3:11])[C:5]([CH:36]2[NH:37][C:32](=[O:31])[CH2:33][CH2:34][CH2:35]2)=[C:6]([O:8][CH3:9])[CH:7]=1

Participants

6

Reactant 4

HCID 6395Methanesulfonic AcidHCID 14812Phosphorus oxide (P4O10)HCID 815021-Chloro-3,5-dimethoxybenzeneHCID 11126383(S)-6-Oxo-2-piperidinecarboxylic acid

Product 1

HCID 690850486-(4-Chloro-2,6-dimethoxyphenyl)piperidin-2-one

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of commercially available 1-chloro-3,5-dimethoxybenzene (1.243 g; 6.98 mmol), P2O5(991 mg; 6.98 mmol), and methanesulfonic acid (5.659 g; 58.89 mmol) was treated with commercially available (S)-6-oxopiperidine-2-carboxylic acid (1.000 g; 6.98 mmol), and the resulting mixture was heated to 100° C. for 30 min. After cooling to rt, water was added, and the resulting solution was extracted with DCM. The mixed organic layers were dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by preparative HPLC afforded 6-(4-chloro-2,6-dimethoxyphenyl)piperidin-2-one as a colorless solid. LC-MS (conditions E): tR=0.61 min.; [M+H]+: 270.26 g/mol.

Workup

  1. temperatureAfter cooling to rt
  2. extractionthe resulting solution was extracted with DCM
  3. dry with materialThe mixed organic layers were dried over anh. MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated to dryness under reduced pressure
  6. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-11dd0bceafb14a0ba3cb616aabca4bb2
Source dataset
uspto-grants-2016_01
Patent number
US09242970B2

Reaction notes

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