Methyl iodide → HCID 71542818, compound

HRID 1776645Notes

Reaction equation

HRID 1776645 reaction equation
[Cl:1][C:2]1[CH:3]=[N+:4]([O-:39])[CH:5]=[C:6]([Cl:38])[C:7]=1[CH2:8][C@@H:9]([C:23]1[CH:28]=[CH:27][C:26]([O:29][CH:30]([F:32])[F:31])=[C:25]([O:33][CH2:34][CH:35]2[CH2:37][CH2:36]2)[CH:24]=1)[O:10][C:11](OC1C=CC([N+]([O-])=O)=CC=1)=[O:12].[CH3:40][O:41][C:42]1[CH:43]=[C:44]([CH2:50][NH2:51])[CH:45]=[CH:46][C:47]=1[O:48][CH3:49].[H-].[Na+].I[CH3:55]>C1COCC1>[Cl:1][C:2]1[CH:3]=[N+:4]([O-:39])[CH:5]=[C:6]([Cl:38])[C:7]=1[CH2:8][C@@H:9]([C:23]1[CH:28]=[CH:27][C:26]([O:29][CH:30]([F:31])[F:32])=[C:25]([O:33][CH2:34][CH:35]2[CH2:36][CH2:37]2)[CH:24]=1)[O:10][C:11](=[O:12])[N:51]([CH2:50][C:44]1[CH:45]=[CH:46][C:47]([O:48][CH3:49])=[C:42]([O:41][CH3:40])[CH:43]=1)[CH3:55]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 79832VeratrylamineHCID 86679418(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((4-nitrophenoxy)-carbonyloxy)ethyl)pyridine 1-oxide

Product 1

HCID 71542818HCID 71542818, compoundYield 29.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((4-nitrophenoxy)carbonyloxy)ethyl)pyridine 1-oxide (for reference procedure see Example 3, Step 1) (300 mg, 0.513 mmol) in dry THF (5 ml), (3,4-dimethoxyphenyl)methanamine (0.077 ml, 0.513 mmol) was added. The mixture was stirred at RT for 2 hours and then cooled to 0° C. NaH (60% w/w dispersion in mineral oil, 61.5 mg, 1.538 mmol) was added portion wise followed by iodomethane (0.080 ml, 1.281 mmol). The cold bath was removed and the reaction was stirred at RT for 5 hours. The mixture was cooled to 0° C., quenched with water and then extracted with EtOAc. The combined organic layers were dried over Na2SO4, the solvent was evaporated, and the crude was purified by flash chromatography on silica gel column (DCM/MeOH 100/2). The desired product was obtained as a white solid (96 mg, 0.153 mmol, 29.9% yield, MS/ESI+ 626.89 [MH]+[αD]=−12.01, c=0.616, DCM).

Workup

  1. temperaturecooled to 0° C
  2. customThe cold bath was removed
  3. stirringthe reaction was stirred at RT for 5 hours
  4. temperatureThe mixture was cooled to 0° C.
  5. customquenched with water
  6. extractionextracted with EtOAc
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. customthe solvent was evaporated
  9. customthe crude was purified by flash chromatography on silica gel column (DCM/MeOH 100/2)

Sources & evidence

ORD record
ord-e6a4b8716aa74a1d804096242f0e3c73
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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