Hydrochloric Acid → (2R)-3-[3-bromo-4-(1,1-dioxido-3-oxoisothiazolidin-5-yl)phenyl]-2-[(phenylsulfonyl)-amino]propanoic Acid

HRID 724664Notes

Reaction equation

HRID 724664 reaction equation
FC(F)(F)C(O)=O.[NH2:8][C@@H:9]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([CH:21]2[S:25](=[O:27])(=[O:26])[NH:24][C:23](=[O:28])[CH2:22]2)=[C:17]([Br:29])[CH:16]=1)[C:10]([O:12]C)=[O:11].C(N(CC)CC)C.[C:37]1([S:43](Cl)(=[O:45])=[O:44])[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.[OH-].[Li+].Cl>CO.O>[Br:29][C:17]1[CH:16]=[C:15]([CH2:14][C@@H:9]([NH:8][S:43]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)(=[O:45])=[O:44])[C:10]([OH:12])=[O:11])[CH:20]=[CH:19][C:18]=1[CH:21]1[S:25](=[O:27])(=[O:26])[NH:24][C:23](=[O:28])[CH2:22]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 7369Benzenesulfonyl chlorideHCID 8471TriethylamineHCID 11670631Methyl (2S)-2-amino-3-[3-bromo-4-(1,1-dioxido-3-oxoisothiazolidin-5-yl)phenyl]-propanoate Trifluoroacetate

Product 1

HCID 69597645(2R)-3-[3-bromo-4-(1,1-dioxido-3-oxoisothiazolidin-5-yl)phenyl]-2-[(phenylsulfonyl)-amino]propanoic AcidYield 70.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 962WaterSolvent

Procedure

Methyl (2S)-2-amino-3-[3-bromo-4-(1,1-dioxido-3-oxoisothiazolidin-5-yl)-phenyl]-propanoate trifluoroacetate (77.1 mg, 0.152 mmol) in methanol (1.7 mL,) was treated with triethylamine (85.0 μL, 0.610 mmol) and then benzenesulfonyl chloride (29.2 μL, 0.228 mmol). The solution was stirred at rt for 2 h. 4 M lithium hydroxide in water (0.38 mL) was added and stirred for 3 h at rt. The solution was acidified with aqueous 1 N hydrochloric acid solution (4 mL), diluted with methanol (1.5 mL) and purified by preparative LCMS to afford product as a white solid (55.4 mg, 70%). 1H NMR (400 MHz, CD3OD): δ 7.65–7.62 (m, 2H), 7.53–7.36 (m, 4H), 7.25–7.20 (m, 1H), 5.65 (t, J=6.8 Hz, 1H), 4.06–5.01 (m, 1H), 3.48 (dd, J=16.2, 8.0 Hz, 1H), 3.38–3.28 (m, 1H), 3.11–3.06 (m, 1H), 2.87–2.83 (m, 1H); LCMS found for C18H18BrN2O7S2 (M+H)+: m/z=517.

Workup

  1. stirringstirred for 3 h at rt
  2. custompurified by preparative LCMS

Sources & evidence

ORD record
ord-fd98c279e8074310afce4367d104a61a
Source dataset
uspto-grants-2006_11
Patent number
US07141596B2

Reaction notes

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