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

HRID 522577Notes

Reaction equation

HRID 522577 reaction equation
[C:1]1(C2SCC(C(O)=O)N=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.N1C2C(=CC(C#N)=CC=2)C=C1.[NH:26]1[C:34]2[C:29](=[CH:30][C:31]([C:35]3[S:36][CH2:37][C@@H:38]([C:40]([OH:42])=[O:41])[N:39]=3)=[CH:32][CH:33]=2)[CH:28]=[CH:27]1.[OH-].[Na+].[S:45](Cl)(Cl)(=[O:47])=[O:46].Cl>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[NH:26]1[C:34]2[C:29](=[CH:30][C:31]([C:35]3[S:36][CH2:37][C@@H:38]([C:40]([OH:42])=[O:41])[N:39]=3)=[CH:32][CH:33]=2)[CH:28]=[CH:27]1.[C:1]1([S:45]([N:26]2[C:34]3[C:29](=[CH:30][C:31]([C:35]4[S:36][CH2:37][C@@H:38]([C:40]([OH:42])=[O:41])[N:39]=4)=[CH:32][CH:33]=3)[CH:28]=[CH:27]2)(=[O:47])=[O:46])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 24648Sulfuryl chlorideHCID 27513Indole-5-carbonitrileHCID 883272-Phenyl-4,5-dihydro-1,3-thiazole-4-carboxylic acidHCID 53363877(R)-2-(1H-indol-5-yl)-4,5-dihydrothiazole-4-carboxylic acid

Product 2

HCID 53363877(R)-2-(1H-indol-5-yl)-4,5-dihydrothiazole-4-carboxylic acidHCID 53363878(R)-2-(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 using the same method as used for 42a from 1H-indole-5-carbonitrile and used without further 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. customused without further 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-fb07e839609548c897f235939aa12d99
Source dataset
uspto-grants-2016_05
Patent number
US09334242B2

Reaction notes

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