Phosphate → 4,5-dihydro-2-(2,4-dihydroxyphenyl)-thiazole-4(S)-carboxylic acid

HRID 857083

Reaction equation

HRID 857083 reaction equation
O.Cl.[NH2:3][C@@H:4]([C:7]([OH:9])=[O:8])[CH2:5][SH:6].[OH:10][C:11]1[CH:18]=[C:17]([OH:19])[CH:16]=[CH:15][C:12]=1[C:13]#N.P([O-])([O-])([O-])=O.C([O-])(O)=O.[Na+]>CO>[OH:10][C:11]1[CH:18]=[C:17]([OH:19])[CH:16]=[CH:15][C:12]=1[C:13]1[S:6][CH2:5][C@H:4]([C:7]([OH:9])=[O:8])[N:3]=1

Participants

6

Reactant 4

HCID 1061PhosphateHCID 516892Sodium BicarbonateHCID 30175202,4-DihydroxybenzonitrileHCID 10176341D-Cysteine hydrochloride monohydrate

Product 1

HCID 1355326814,5-dihydro-2-(2,4-dihydroxyphenyl)-thiazole-4(S)-carboxylic acidYield 66%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

D-cysteine hydrochloride monohydrate (6.8 g, 38.7 mmol) was added to a solution of 2,4dihydroxybenzonitrile (3.5 g, 25.9 mmol), prepared as described above, in a mixture of degassed methanol (105 ml) and 0.1 M phosphate buffer, pH 5.95 (70 ml). NaHCO3 (3.25 g, 38.7 mmol) was carefully added and the mixture was stirred at 70° C. under Argon for 54 hours. Volatile components were removed under reduced pressure and the solution was acidified with 1 N HCl to pH 2. The resulting brown precipitate was vacuum filtered and the solid was washed with water (40 ml) and ethanol (20 ml). The crude product was dissolved in saturated NaHCO3 (700 ml) and the aqueous solution washed with ethyl acetate (2×200 ml). The aqueous layer was filtered through a fine frit and acidified with 1 N HCl to pH 2. The precipitated product was vacuum filtered. The aqueous layer was extracted with ethyl acetate (4×400 ml), the combined organic extracts were dried (Na2SO4) and the solvent was removed in vacuo. The remaining solid was combined with the precipitated product and dried under high vacuum at 40° C. for 12 hours to give 4,5-dihydro-2-(2,4-dihydroxyphenyl)-thiazole-4(S)-carboxylic acid (4.08 g, 66%), mp 266–268° C. (dec) (Ind. J. Chem., Vol. 15B, Kishore et al, pages 255–257 (1977) for (L)-isomer: 261–262° C.). 1H NMR (300 MHz, DMSO-d6) δ 3.61 (m, 2 H), 5.38 (dd, 1 H, J=7.2/9.4 Hz), 6.31 (d, 1 H, J=2.3 Hz), 6.38 (dd, 1 H, J=2.3/8.6 Hz), 7.25 (d, 1 H, J=8.6 Hz), 10.25 (br s, 1 H), 12.60 (br s, 1 H), 13.15 (br s, 1 H). Anal. Calc. For C10H9NO4S: C 50.20, H 3.79, N 5.85. Found: C 50.13, H 3.82, N 5.85.

Workup

  1. customprepared
  2. customVolatile components were removed under reduced pressure
  3. filtrationfiltered
  4. washthe solid was washed with water (40 ml) and ethanol (20 ml)
  5. dissolutionThe crude product was dissolved in saturated NaHCO3 (700 ml)
  6. washthe aqueous solution washed with ethyl acetate (2×200 ml)
  7. filtrationThe aqueous layer was filtered through a fine frit
  8. filtrationfiltered
  9. extractionThe aqueous layer was extracted with ethyl acetate (4×400 ml)
  10. dry with materialthe combined organic extracts were dried (Na2SO4)
  11. customthe solvent was removed in vacuo
  12. customdried under high vacuum at 40° C. for 12 hours

Sources & evidence

ORD record
ord-c65e7c7dad4749dd9c9ddb71cb457630
Source dataset
uspto-grants-2006_12
Patent number
US07144904B2

Linked notes

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