Methyl iodide → HCID 71542819, compound

HRID 1776625Notes

Reaction equation

HRID 1776625 reaction equation
[Cl:1][C:2]1[CH:3]=[N+:4]([O-:40])[CH:5]=[C:6]([Cl:39])[C:7]=1[CH2:8][C@@H:9]([C:24]1[CH:29]=[CH:28][C:27]([O:30][CH:31]([F:33])[F:32])=[C:26]([O:34][CH2:35][CH:36]2[CH2:38][CH2:37]2)[CH:25]=1)[O:10][C:11](=[O:23])[NH:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][CH3:22])[CH:14]=1.[H-].[Na+].I[CH3:44]>C1COCC1>[Cl:1][C:2]1[CH:3]=[N+:4]([O-:40])[CH:5]=[C:6]([Cl:39])[C:7]=1[CH2:8][C@@H:9]([C:24]1[CH:29]=[CH:28][C:27]([O:30][CH:31]([F:33])[F:32])=[C:26]([O:34][CH2:35][CH:36]2[CH2:38][CH2:37]2)[CH:25]=1)[O:10][C:11](=[O:23])[N:12]([C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][CH3:22])[CH:14]=1)[CH3:44]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 86679582HCID 86679582, compound

Product 1

HCID 71542819HCID 71542819, compoundYield 73.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3,4-dimethoxyphenylcarbamoyloxy)ethyl)pyridine 1-oxide (127.5 mg, 0.21 mmol) in anhydrous THF (4 ml) and cooled at 0° C., sodium hydride (10.21 mg, 0.255 mmol) and iodomethane (0.016 ml, 0.255 mmol) were sequentially added. The cold bath was removed and the mixture was stirred at RT for 2 hours. Then the reaction was quenched with iced water and extracted with EtOAc. The combined organic layer were washed with brine, dried over Na2SO4 and evaporated. Purification of the resulting crude by flash chromatography on silica gel (DCM:MeOH 100:2) afforded the desired product as a white solid (95 mg, 0.155 mmol, 72.8% yield, [α]D=+21.41, c 0.569, DCM)

Workup

  1. customThe cold bath was removed
  2. customThen the reaction was quenched with iced water
  3. extractionextracted with EtOAc
  4. washThe combined organic layer were washed with brine
  5. dry with materialdried over Na2SO4
  6. customevaporated
  7. customPurification of the resulting crude by flash chromatography on silica gel (DCM:MeOH 100:2)

Sources & evidence

ORD record
ord-9e41e8aa352e49f99c5583e62ab16365
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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