Iodine → 3,4-dichloro-5-methyl-N-[(3S,4R)-3-(prop-2-en-1-yloxy)piperidin-4-yl]-1H-pyrrole-2-carboxamide

HRID 655757Notes

Reaction equation

HRID 655757 reaction equation
[Cl:1][C:2]1[C:6]([Cl:7])=[C:5]([CH3:8])[NH:4][C:3]=1[C:9]([NH:11][C@@H:12]1[CH2:17][CH2:16][N:15](C(OCC)=O)[CH2:14][C@@H:13]1[O:23][CH2:24][CH:25]=[CH2:26])=[O:10].II.C[Si](C)(C)[Si](C)(C)C.S([O-])([O-])(=O)=S.[Na+].[Na+]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:6]([Cl:7])=[C:5]([CH3:8])[NH:4][C:3]=1[C:9]([NH:11][C@@H:12]1[CH2:17][CH2:16][NH:15][CH2:14][C@@H:13]1[O:23][CH2:24][CH:25]=[CH2:26])=[O:10]

Participants

6

Reactant 4

HCID 807IodineHCID 24477Sodium ThiosulfateHCID 74057HexamethyldisilaneHCID 59402556Ethyl (3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-(prop-2-en-1-yloxy)piperidine-1-carboxylate2×

Product 1

HCID 594024493,4-dichloro-5-methyl-N-[(3S,4R)-3-(prop-2-en-1-yloxy)piperidin-4-yl]-1H-pyrrole-2-carboxamideYield 36.54%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To as solution of Ethyl (3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-(prop-2-en-1-yloxy)piperidine-1-carboxylate (Intermediate 19, 2.5 g, 6.20 mmol) in toluene (450 mL) was added iodine (6.31 g, 24.8 mmol) followed by hexamethyldisilane (10.34 mL, 49.62 mmol and the reaction mixture was refluxed for 30 h. The reaction mixture was treated with 10% sodium thiosulphate (300 mL) and layers were separated. The aqueous layer was extracted with toluene and the organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure. Purification by column chromatography (silica, 4% methanol in dichloromethane) afforded 750 mg (36.54%) of 3,4-dichloro-5-methyl-N-[(3S,4R)-3-(prop-2-en-1-yloxy)piperidin-4-yl]-1H-pyrrole-2-carboxamide.

Workup

  1. temperaturethe reaction mixture was refluxed for 30 h
  2. customwere separated
  3. extractionThe aqueous layer was extracted with toluene
  4. dry with materialthe organic layer was dried over anhydrous sodium sulphate
  5. concentrationconcentrated under reduced pressure
  6. customPurification by column chromatography (silica, 4% methanol in dichloromethane)

Sources & evidence

ORD record
ord-b3875975125d4fbc88c8f958563a104d
Source dataset
uspto-grants-2011_12
Patent number
US08071605B2

Reaction notes

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