Water → Ureidovaline

HRID 1275353Notes

Reaction equation

HRID 1275353 reaction equation
[H-].[Na+].[CH3:3][NH:4][CH2:5][C:6]1[N:7]=[C:8]([CH:11]([CH3:13])[CH3:12])[S:9][CH:10]=1.[O:14]([C:21]([NH:23][C@H:24]([C:28]([OH:30])=[O:29])[CH:25]([CH3:27])[CH3:26])=O)C1C=CC=CC=1.O>C1COCC1>[CH3:3][N:4]([C:21]([NH:23][C@H:24]([C:28]([OH:30])=[O:29])[CH:25]([CH3:27])[CH3:26])=[O:14])[CH2:5][C:6]1[N:7]=[C:8]([CH:11]([CH3:13])[CH3:12])[S:9][CH:10]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 9816135N-Phenoxycarbonyl-L-valineHCID 107496872-Isopropyl-4-(N-methyl)amino-methyl thiazole

Product 1

HCID 9818282UreidovalineYield 83%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Conditions

Temperature
50 °C

Procedure

To a stirred slurry of 95% NaH (560 mg, 23.2 mmol) at -10° C. in 20 mL of THF was slowly added N-methyl-N-((2-isopropyl-4-thiazolyl)methyl)amine (3.76 g, 22.1 mmol) keeping the temperature not more than 0° C. THF (5 mL) was added as a rinse. A solution of N-phenoxycarbonyl-L-Valine (5.0 g, 21.1 mmol) dissolved in 20 mL of THF was added slowly keeping the temperature not more than 0° C. THF (5 mL) was added as a rinse. After 4 hours, water (100 mL) was added, and the THF was removed under reduced pressure. The pH was adjusted to 9 with concentrated HCl, and the phenol by-product was removed with methyl tert-butyl ether washes (3×60 mL). The aqueous phase was stirred with 70 mL of toluene and adjusted to pH 3 with 4 N HCl. The aqueous phase was separated and extracted twice more with toluene (2×70 mL). The combined toluene extracts were concentrated under reduced pressure, and the residue was redissolved in toluene and heptane (50 mLs of a 1:1 v/v solution), warmed to 50° C. and allowed to cool to ambient temperature. The product was collected by filtration, washed with heptane and dried under vacuum to afford the title compound as a white powder in 83% yield.

Workup

  1. customat -10° C.
  2. customthe temperature not more than 0° C
  3. additionwas added slowly
  4. customthe temperature not more than 0° C
  5. customthe THF was removed under reduced pressure
  6. customthe phenol by-product was removed with methyl tert-butyl ether washes (3×60 mL)
  7. customThe aqueous phase was separated
  8. extractionextracted twice more with toluene (2×70 mL)
  9. concentrationThe combined toluene extracts were concentrated under reduced pressure
  10. dissolutionthe residue was redissolved in toluene
  11. temperatureto cool to ambient temperature
  12. filtrationThe product was collected by filtration
  13. washwashed with heptane
  14. customdried under vacuum

Sources & evidence

ORD record
ord-66fb0eff1fec4406a4494de3dd8236b6
Source dataset
uspto-grants-2000_12
Patent number
US06160122

Reaction notes

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