Water → Ureidovaline

HRID 1275356Notes

Reaction equation

HRID 1275356 reaction equation
C1(O)C=CC=CC=1.[CH3:8][NH:9][CH2:10][C:11]1[N:12]=[C:13]([CH:16]([CH3:18])[CH3:17])[S:14][CH:15]=1.[O:19]([C:26]([NH:28][C@H:29]([C:33]([OH:35])=[O:34])[CH:30]([CH3:32])[CH3:31])=O)C1C=CC=CC=1.O>C1COCC1>[CH3:8][N:9]([C:26]([NH:28][C@H:29]([C:33]([OH:35])=[O:34])[CH:30]([CH3:32])[CH3:31])=[O:19])[CH2:10][C:11]1[N:12]=[C:13]([CH:16]([CH3:18])[CH3:17])[S:14][CH:15]=1

Participants

6

Reactant 4

HCID 962WaterHCID 996PhenolHCID 9816135N-Phenoxycarbonyl-L-valineHCID 107496872-Isopropyl-4-(N-methyl)amino-methyl thiazole

Product 1

HCID 9818282UreidovalineYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
4.5 °C

Procedure

To a solution of LiOH monohydrate (970 mg, 23.2 mmol) and phenol (2.18 g, 23.2 mmol) dissolved in 25 mL of THF and cooled with an ice bath to 3-6° C. was added N-methyl-N-((2-isopropyl-4-thiazolyl)methyl)amine (3.95 g, 23.2 mmol) followed by a 1 mL THF rinse. To this mixture was slowly added a solution of N-phenoxycarbonyl-L-Valine (5.0 g, 21.1 mmol) dissolved in 20 mL of THF maintaining the temperature between 3° C. and 8° C. Following the addition and a 5 mL THF rinse, the cooling bath was removed, and the reaction was allowed to warm to ambient temperature. After stirring for 3 hours at ambient temperature, an additional aliquot of LiOH monohydrate (440 mg, 10.4 mmol) was added. One hour later, the reaction was treated with 100 mL of water and the THF removed under reduced pressure. The aqueous phase was adjusted to pH 9 using concentrated HCl and then washed with MTBE (3×60 mL). Toluene (60 mL) was added to the aqueous phase which was then acidified to pH 2.5 using 4 N HCl. The toluene phase was separated, and the aqueous phase was back extracted with four 60 mL aliquots of toluene. The combined organic extracts were concentrated under reduced pressure. The oil obtained was crystallized from toluene-heptane to give the title compound (5.41 g, 82%).

Workup

  1. washrinse
  2. additionthe addition
  3. washa 5 mL THF rinse
  4. customthe cooling bath was removed
  5. temperatureto warm to ambient temperature
  6. customthe THF removed under reduced pressure
  7. washwashed with MTBE (3×60 mL)
  8. additionToluene (60 mL) was added to the aqueous phase which
  9. customThe toluene phase was separated
  10. extractionthe aqueous phase was back extracted with four 60 mL aliquots of toluene
  11. concentrationThe combined organic extracts were concentrated under reduced pressure
  12. customThe oil obtained
  13. customwas crystallized from toluene-heptane

Sources & evidence

ORD record
ord-4512ec0b4ae7494c8e90066fc9a23721
Source dataset
uspto-grants-2000_12
Patent number
US06160122

Reaction notes

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