Phosphate → 2-Phenyl-4,5-dihydro-1,3-thiazole-4-carboxylic acid

HRID 572460Notes

Reaction equation

HRID 572460 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]#[N:11])=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[C:12]1([C:18]2[S:19][CH2:20][CH:21]([C:23]([OH:25])=[O:24])[N:22]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(#N)C1C=CC=CC=1.N[C@H](C(O)=O)CS.P([O-])([O-])([O-])=O>CO>[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]3[S:19][CH2:20][C@@H:21]([C:23]([OH:25])=[O:24])[N:11]=3)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[C:12]1([C:18]2[S:19][CH2:20][CH:21]([C:23]([OH:25])=[O:24])[N:22]=2)[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

8

Reactant 5

HCID 1061PhosphateHCID 5862L-(+)-CysteineHCID 7505BenzonitrileHCID 27513Indole-5-carbonitrileHCID 883272-Phenyl-4,5-dihydro-1,3-thiazole-4-carboxylic acid

Product 2

HCID 883272-Phenyl-4,5-dihydro-1,3-thiazole-4-carboxylic acidHCID 53363877(R)-2-(1H-indol-5-yl)-4,5-dihydrothiazole-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
40 °C

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. customThe precipitate was removed by filtration, and MeOH
  2. customwas removed
  3. customevaporation
  4. additionTo the remaining solution was added 1 M HCl
  5. customto adjust to pH=2 under 0° C
  6. filtrationThe resulting precipitate was filtered

Sources & evidence

ORD record
ord-dca4b35a6ae44a2eb53b33d0cbab224b
Source dataset
uspto-grants-2015_05
Patent number
US09029408B2

Reaction notes

Loading…