Hydrochloric Acid → HCID 58746551, compound

HRID 724672Notes

Reaction equation

HRID 724672 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]([Cl: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>FC(F)(F)C(O)=O.CO>[Cl: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 86602078HCID 86602078, compound

Product 1

HCID 58746551HCID 58746551, compoundYield 73%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
130 °C

Procedure

Methyl (2S)-2-amino-3-[3-chloro-4-(1,1-dioxido-3-oxoisothiazolidin-5-yl)-phenyl]-propanoate trifluoroacetate (145 mg, 0.314 mmol) was dissolved in trifluoroacetic acid (3 mL) and heated in the microwave at 130° C. for 180 s. The reaction was concentrated in vacuo and azetroped with toluene (5 mL). The product was dissolved in methanol (2 mL), was treated with triethylamine (170 μL, 1.2 mmol) and then benzenesulfonyl chloride (60 μL, 0.47 mmol). The solution stirred at rt for 1 h. 4 M aqueous lithium hydroxide solution (0.782 mL) was added and the solution stirred 3 h at rt. The solution was acidified with aqueous hydrochloric acid solution (1.0 N, 4.0 mL), diluted with methanol to 10 mL volume, and then purified by reverse phase HPLC to afford product as a white solid (108 mg, 73%). 1H NMR (400 MHz, CD3OD): δ 7.66–7.64 (m, 2H), 7.63–7.51 (m, 1H), 7.44–7.38 (m, 3H), 7.31–7.16 (m, 2H), 5.65–5.61 (m, 1H), 4.10–4.03 (m, 1H), 3.48–3.42 (m, 1H), 3.29–3.27 (m, 1H), 3.12–3.07 (m, 1H), 2.88–2.81 (m, 1H); LCMS found for C18H21ClN3O7S2 (M+H)+: m/z=490.

Workup

  1. concentrationThe reaction was concentrated in vacuo and azetroped with toluene (5 mL)
  2. dissolutionThe product was dissolved in methanol (2 mL)
  3. stirringthe solution stirred 3 h at rt
  4. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-90c7b9d74cc648d98d34697de9aedc46
Source dataset
uspto-grants-2006_11
Patent number
US07141596B2

Reaction notes

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