Potassium Carbonate → (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(N-(2-(methoxycarbonyl)phenyl)-methylsulfonamido)acetoxy)ethyl)pyridine 1-oxide

HRID 1776605Notes

Reaction equation

HRID 1776605 reaction equation
Br[CH2:2][C:3]([O:5][C@H:6]([C:17]1[CH:22]=[CH:21][C:20]([O:23][CH:24]([F:26])[F:25])=[C:19]([O:27][CH2:28][CH:29]2[CH2:31][CH2:30]2)[CH:18]=1)[CH2:7][C:8]1[C:13]([Cl:14])=[CH:12][N+:11]([O-:15])=[CH:10][C:9]=1[Cl:16])=[O:4].BrCC(O[C@H](C1C=CC(OC(F)F)=C(OCC2CC2)C=1)CC1C(Cl)=CN=CC=1Cl)=O.C([O-])([O-])=O.[K+].[K+].[CH3:68][S:69]([NH:72][C:73]1[CH:82]=[CH:81][CH:80]=[CH:79][C:74]=1[C:75]([O:77][CH3:78])=[O:76])(=[O:71])=[O:70]>CN(C=O)C.O>[Cl:16][C:9]1[CH:10]=[N+:11]([O-:15])[CH:12]=[C:13]([Cl:14])[C:8]=1[CH2:7][C@@H:6]([C:17]1[CH:22]=[CH:21][C:20]([O:23][CH:24]([F:26])[F:25])=[C:19]([O:27][CH2:28][CH:29]2[CH2:31][CH2:30]2)[CH:18]=1)[O:5][C:3](=[O:4])[CH2:2][N:72]([C:73]1[CH:82]=[CH:81][CH:80]=[CH:79][C:74]=1[C:75]([O:77][CH3:78])=[O:76])[S:69]([CH3:68])(=[O:71])=[O:70]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 669032Methyl 2-[(methylsulfonyl)amino]benzoateHCID 86679564(S)-4-(2-(2-bromoacetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxideHCID 86679565(S)-4-(2-(2-bromoacetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine

Product 1

HCID 71543011(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(2-(N-(2-(methoxycarbonyl)phenyl)-methylsulfonamido)acetoxy)ethyl)pyridine 1-oxideYield 85%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

The mixture obtained in step 2, containing (S)-4-(2-(2-bromoacetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine (100 mg) was dissolved in DMF (2 ml), and K2CO3 (30 mg, 0.22 mmol) and methyl 2-(methylsulfonamido)benzoate (82 mg, 0.36 mmol) were added. The mixture was stirred at RT for 5 hours. The reaction was diluted with water, and the product was extracted with EtOAc. The organic layer was washed with water, dried over Na2SO4 and evaporated under vacuum. The crude product was purified by preparative reverse-phase HPLC to give 105 mg of the desired product (Yield: 85%, MS/ESI+ 689.5 [MH]+).

Workup

  1. extractionthe product was extracted with EtOAc
  2. washThe organic layer was washed with water
  3. dry with materialdried over Na2SO4
  4. customevaporated under vacuum
  5. customThe crude product was purified by preparative reverse-phase HPLC

Sources & evidence

ORD record
ord-202a7a74683f4aa4a1e53658a1d99efc
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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