1,2-Dichloroethane → (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)-phenyl)-2-(3-(methylsulfonamido)thiophene-2-carbonyloxy)ethyl)pyridine 1-oxide

HRID 59737Notes

Reaction equation

HRID 59737 reaction equation
[CH3:1][S:2]([NH:5][C:6]1[CH:10]=[CH:9][S:8][C:7]=1[C:11]([OH:13])=[O:12])(=[O:4])=[O:3].[Cl:14][C:15]1[CH:16]=[N+:17]([O-:40])[CH:18]=[C:19]([Cl:39])[C:20]=1[CH2:21][C@@H:22]([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.C(Cl)CCl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Cl:14][C:15]1[CH:16]=[N+:17]([O-:40])[CH:18]=[C:19]([Cl:39])[C:20]=1[CH2:21][C@@H:22]([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:12][C:11]([C:7]1[S:8][CH:9]=[CH:10][C:6]=1[NH:5][S:2]([CH3:1])(=[O:3])=[O:4])=[O:13]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 167739453-Methanesulfonamidothiophene-2-carboxylic acidHCID 71092687(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide

Product 1

HCID 72706758(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)-phenyl)-2-(3-(methylsulfonamido)thiophene-2-carbonyloxy)ethyl)pyridine 1-oxideYield 30.6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 3-(methylsulfonamido)thiophene-2-carboxylic acid (Int. 38) (110 mg, 0.497 mmol), (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)-phenyl)-2-hydroxyethyl)pyridine 1-oxide (209 mg, 0.497 mmol), EDC (286 mg, 1.491 mmol) and DMAP (30.4 mg, 0.249 mmol) in DCM (25 ml) was stirred at RT for 3 days. The mixture was diluted with DCM and washed with 1N HCl and aqueous NaHCO3; the organic layer was dried over Na2SO4, filtered and evaporated. The crude was purified by flash chromatography on silica gel cartridge (DCM/MeOH=99.5/0.5 to 99/1) affording (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)-phenyl)-2-(3-(methylsulfonamido)thiophene-2-carbonyloxy)ethyl)pyridine 1-oxide (Int. 39) (95 mg, 0.152 mmol, MS/ESI+623.05 [MH]+, [αD]=−28.6, c=0.3, DCM).

Workup

  1. washwashed with 1N HCl and aqueous NaHCO3
  2. dry with materialthe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. customevaporated
  5. customThe crude was purified by flash chromatography on silica gel cartridge (DCM/MeOH=99.5/0.5 to 99/1)

Sources & evidence

ORD record
ord-242719a229a24142be1434d632b1633f
Source dataset
uspto-grants-2016_09
Patent number
US09440954B2

Reaction notes

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