Benzoic acid, 3-(chlorosulfonyl)- → 4-((S)-2-((S)-3-(3-carboxyphenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide

HRID 1754309Notes

Reaction equation

HRID 1754309 reaction equation
[Cl:1][C:2]1[CH:3]=[N+:4]([O-:34])[CH:5]=[C:6]([Cl:33])[C:7]=1[CH2:8][C@@H:9]([C:18]1[CH:23]=[CH:22][C:21]([O:24][CH:25]([F:27])[F:26])=[C:20]([O:28][CH2:29][CH:30]2[CH2:32][CH2:31]2)[CH:19]=1)[O:10][C:11]([C@H:13]1[NH:17][CH2:16][CH2:15][S:14]1)=[O:12].Cl[S:36]([C:39]1[CH:40]=[C:41]([CH:45]=[CH:46][CH:47]=1)[C:42]([OH:44])=[O:43])(=[O:38])=[O:37]>N1C=CC=CC=1.Cl>[C:42]([C:41]1[CH:40]=[C:39]([S:36]([N:17]2[CH2:16][CH2:15][S:14][C@H:13]2[C:11]([O:10][C@H:9]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH:25]([F:27])[F:26])=[C:20]([O:28][CH2:29][CH:30]3[CH2:32][CH2:31]3)[CH:19]=2)[CH2:8][C:7]2[C:6]([Cl:33])=[CH:5][N+:4]([O-:34])=[CH:3][C:2]=2[Cl:1])=[O:12])(=[O:38])=[O:37])[CH:47]=[CH:46][CH:45]=1)([OH:44])=[O:43]

Participants

5

Reactant 2

HCID 77641Benzoic acid, 3-(chlorosulfonyl)-HCID 710925213,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide

Product 1

HCID 710924964-((S)-2-((S)-3-(3-carboxyphenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxideYield 35.6%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 1049PyridineSolvent

Procedure

3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide (209 mg, 0.390 mmol) was dissolved in pyridine (4 ml). 3-(chlorosulfonyl)benzoic acid (172 mg, 0.781 mmol) was added slowly at 0° C., and the reaction was stirred at RT for 8 hours. The reaction mixture was diluted with HCl 1N, filtered, and the precipitate was dissolved in DCM. The organic phase was washed with HCl 1N (2×) and brine, dried over Na2SO4 and concentrated under vacuum to give 4-((S)-2-((S)-3-(3-carboxyphenylsulfonyl)thiazolidine-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (100 mg, 0.139 mmol, 35.6% yield), that was used in the next step without any further purification.

Workup

  1. filtrationfiltered
  2. dissolutionthe precipitate was dissolved in DCM
  3. washThe organic phase was washed with HCl 1N (2×) and brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-27ebb99bd83a4a518ab2260a7429012c
Source dataset
uspto-grants-2015_10
Patent number
US09169245B2

Reaction notes

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