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

HRID 655759Notes

Reaction equation

HRID 655759 reaction equation
[Cl:1][C:2]1[C:3]([C:26]#[N:27])=[C:4]([C:8]([NH:10][C@@H:11]2[CH2:16][CH2:15][N:14](C(OCC)=O)[CH2:13][C@@H:12]2[O:22][CH2:23][CH:24]=[CH2:25])=[O:9])[NH:5][C:6]=1[CH3:7].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:3]([C:26]#[N:27])=[C:4]([C:8]([NH:10][C@@H:11]2[CH2:16][CH2:15][NH:14][CH2:13][C@@H:12]2[O:22][CH2:23][CH:24]=[CH2:25])=[O:9])[NH:5][C:6]=1[CH3:7]

Participants

6

Reactant 4

HCID 807IodineHCID 24477Sodium ThiosulfateHCID 74057HexamethyldisilaneHCID 59402444HCID 59402444, compound2×

Product 1

HCID 594025964-chloro-3-cyano-5-methyl-N-[(3S,4R)-3-(prop-2-en-1-yloxy)piperidin-4-yl]-1H-pyrrole-2-carboxamideYield 33.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To as solution of ethyl (3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-(prop-2-en-1-yloxy)piperidine-1-carboxylate (Intermediate 21, 1.1 g, 2.79 mmol) in toluene (190 mL) was added iodine (2.9 g, 11.16 mmol) followed by hexamethyldisilane (4.65 mL, 22.33 mmol). The reaction mixture was heated to reflux for 30 h and then cooled to room temperature. The reaction mixture was treated 10% sodium thiosulphate (150 mL) and the 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 300 mg (33%) of 4-chloro-3-cyano-5-methyl-N-[(3S,4R)-3-(prop-2-en-1-yloxy)piperidin-4-yl]-1H-pyrrole-2-carboxamide

Workup

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

Sources & evidence

ORD record
ord-51c0382585ff426ead7be86c68e881f1
Source dataset
uspto-grants-2011_12
Patent number
US08071605B2

Reaction notes

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