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 520339Notes

Reaction equation

HRID 520339 reaction equation
Cl.[CH:2]1([CH2:5][O:6][C:7]2[CH:8]=[C:9]([C@@H:17]([O:28][C:29]([C@H:31]3[NH:35][CH2:34][CH2:33][S:32]3)=[O:30])[CH2:18][C:19]3[C:24]([Cl:25])=[CH:23][N+:22]([O-:26])=[CH:21][C:20]=3[Cl:27])[CH:10]=[CH:11][C:12]=2[O:13][CH:14]([F:16])[F:15])[CH2:4][CH2:3]1.Cl[S:37]([C:40]1[CH:41]=[C:42]([CH:46]=[CH:47][CH:48]=1)[C:43]([OH:45])=[O:44])(=[O:39])=[O:38]>N1C=CC=CC=1>[C:43]([C:42]1[CH:41]=[C:40]([S:37]([N:35]2[CH2:34][CH2:33][S:32][C@H:31]2[C:29]([O:28][C@H:17]([C:9]2[CH:10]=[CH:11][C:12]([O:13][CH:14]([F:16])[F:15])=[C:7]([O:6][CH2:5][CH:2]3[CH2:4][CH2:3]3)[CH:8]=2)[CH2:18][C:19]2[C:24]([Cl:25])=[CH:23][N+:22]([O-:26])=[CH:21][C:20]=2[Cl:27])=[O:30])(=[O:39])=[O:38])[CH:48]=[CH:47][CH:46]=1)([OH:45])=[O:44]

Participants

4

Reactant 2

HCID 77641Benzoic acid, 3-(chlorosulfonyl)-HCID 710925203,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide hydrochloride2×

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 70%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

3,5-Dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(((S)-thiazolidine-2-carbonyl)oxy)ethyl)pyridine 1-oxide hydrochloride (Intermediate 9 above described) (400 mg, 0,699 mmol) was dissolved in Pyridine (2 ml). 3-(chlorosulfonyl)benzoic acid (463 mg, 2,098 mmol) was added at 0° C., and the reaction was warmed at room temperature for 4 hrs to achieve completion. The reaction mixture was quenched with HCl 1N, and the precipitate was washed with HCl 1N, dissolved in DCM and the organic phase was washed with HCl 1N, water and brine, dried over Na2SO4 and concentrated under vacuum to give 4-((S)-2-(((S)-3-((3-carboxyphenyl)sulfonyl)thiazolidine-2-carbonyl)oxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (352 mg, 0.490 mmol, 70% yield).

Workup

  1. customThe reaction mixture was quenched with HCl 1N
  2. washthe precipitate was washed with HCl 1N
  3. dissolutiondissolved in DCM
  4. washthe organic phase was washed with HCl 1N, water and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-fa1a0c9ac4264b579e2d00a0558ac4c5
Source dataset
uspto-grants-2016_05
Patent number
US09326976B2

Reaction notes

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