N-(4-hydroxyphenyl)methanesulfonamide → (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((4-(methylsulfonamido)-phenoxy)carbonyloxy)ethyl)pyridine 1-oxide

HRID 1776639Notes

Reaction equation

HRID 1776639 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]([O:13][C:14]1[CH:19]=[CH:18][C:17]([N+:20]([O-])=O)=[CH:16][CH:15]=1)=[O:12].OC1C=CC(N[S:48]([CH3:51])(=[O:50])=[O:49])=CC=1>C(Cl)Cl.CN(C1C=CN=CC=1)C>[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]([O:13][C:14]1[CH:19]=[CH:18][C:17]([NH:20][S:48]([CH3:51])(=[O:50])=[O:49])=[CH:16][CH:15]=1)=[O:12]

Participants

5

Reactant 2

HCID 4483147N-(4-hydroxyphenyl)methanesulfonamideHCID 86679418(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((4-nitrophenoxy)-carbonyloxy)ethyl)pyridine 1-oxide

Product 1

HCID 71542732(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((4-(methylsulfonamido)-phenoxy)carbonyloxy)ethyl)pyridine 1-oxideYield 33%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

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 (prepared in an analogous manner to that described in Example 45, Step 4) (0.140 g, 0.239 mmol) in DCM (5 ml), a solution of N-(4-hydroxyphenyl)-methanesulfonamide (0.0672 g, 0.359 mmol) and DMAP (0.0438 g, 0.359 mmol) in DCM (5 ml) was added drop wise, and the reaction was stirred at RT for 3 hours. The solvent was evaporated and the resulting crude was purified by chromatography on silica gel column (DCM:MeOH=10:0.4). A second purification by crystallization from absolute ethanol was required to obtain (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((4-(methylsulfonamido)-phenoxy)carbonyloxy)ethyl)pyridine 1-oxide as a brown solid (0.050 g, 0.079 mmol, 33% yield, MS/ESI+ 632.74 [MH]+, [αD]=−36.59, c=0.252, DCM).

Workup

  1. customThe solvent was evaporated
  2. customthe resulting crude was purified by chromatography on silica gel column (DCM:MeOH=10:0.4)
  3. customA second purification
  4. customby crystallization from absolute ethanol

Sources & evidence

ORD record
ord-a075b8ec098b424f8cb69ca1a1ca395e
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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