Hydrochloric Acid → 2-(1-(Phenylsulfonyl)-1H-indol-5-yl)-4,5-dihydrothiazole-4-carboxylic acid

HRID 572461Notes

Reaction equation

HRID 572461 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]3[S:11][CH2:12][C@@H:13]([C:15]([OH:17])=[O:16])[N:14]=3)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[OH-].[Na+].[S:20](Cl)(Cl)(=[O:22])=[O:21].Cl>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[C:4]1([S:20]([N:1]2[C:9]3[C:4](=[CH:5][C:6]([C:10]4[S:11][CH2:12][CH:13]([C:15]([OH:17])=[O:16])[N:14]=4)=[CH:7][CH:8]=3)[CH:3]=[CH:2]2)(=[O:22])=[O:21])[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 24648Sulfuryl chlorideHCID 53363877(R)-2-(1H-indol-5-yl)-4,5-dihydrothiazole-4-carboxylic acid

Product 1

HCID 667799422-(1-(Phenylsulfonyl)-1H-indol-5-yl)-4,5-dihydrothiazole-4-carboxylic acid

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 1140TolueneSolvent

Procedure

(R)-2-(1H-Indol-5-yl)-4,5-dihydrothiazole-4-carboxylic acid 63a was synthesized from 1H-indole-5-carbonitrile using the same method as used for 42a of U.S. application Ser. No. 12/981,233 (now US2011/0257196) and U.S. application Ser. No. 1/216,927 (now US2012/0071524), incorporated herein by reference in their entirety. Briefly, benzonitrile (40 mmol) was combined with L-cysteine (45 mmol) in 100 mL of 1:1 MeOH/pH 6.4 phosphate buffer solution. The reaction was stirred at 40° C. for 3 days. The precipitate was removed by filtration, and MeOH was removed using rotary evaporation. To the remaining solution was added 1 M HCl to adjust to pH=2 under 0° C. The resulting precipitate was filtered to yield a white solid 2-phenyl-4,5-dihydrothiazole-4-carboxylic acid 42a, which was used directly to next step without purification. To a vigorously stirring solution of 63a (1 mmol) and tetrabutylammonium hydrogen sulfate (0.15 mmol) in toluene (10 mL) at 0° C. was added 50% aqueous sodium hydroxide (10 mL) and sulfonyl chloride (2 mmol). The resultant solution was stirred at RT for 6 h. Then 1 N HCl was added to acidify the mixture to pH=2 and extracted with CH2Cl2, the organic layer was separated and dried (MgSO4); then evaporated to dryness to yield 64a, which were used in subsequent steps without further purification.

Workup

  1. customwas used directly to next step without purification
  2. extractionextracted with CH2Cl2
  3. customthe organic layer was separated
  4. dry with materialdried (MgSO4)
  5. customthen evaporated to dryness

Sources & evidence

ORD record
ord-ca99a6693fd74effbbbdf5e590a32146
Source dataset
uspto-grants-2015_05
Patent number
US09029408B2

Reaction notes

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