Lithium hydroxide, monohydrate → Ureidovaline

HRID 1275354Notes

Reaction equation

HRID 1275354 reaction equation
O.[OH-].[Li+].[CH3:4][NH:5][CH2:6][C:7]1[N:8]=[C:9]([CH:12]([CH3:14])[CH3:13])[S:10][CH:11]=1.[O:15]([C:22]([NH:24][C@H:25]([C:29]([OH:31])=[O:30])[CH:26]([CH3:28])[CH3:27])=O)C1C=CC=CC=1>C1COCC1.C1(C)C=CC=CC=1>[CH3:4][N:5]([C:22]([NH:24][C@H:25]([C:29]([OH:31])=[O:30])[CH:26]([CH3:28])[CH3:27])=[O:15])[CH2:6][C:7]1[N:8]=[C:9]([CH:12]([CH3:14])[CH3:13])[S:10][CH:11]=1

Participants

6

Reactant 3

HCID 168937Lithium hydroxide, monohydrateHCID 9816135N-Phenoxycarbonyl-L-valineHCID 107496872-Isopropyl-4-(N-methyl)amino-methyl thiazole

Product 1

HCID 9818282Ureidovaline

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent4×

Procedure

To lithium hydroxide monohydrate (1.06 g, 25.2 mmol) slurried in 20 mL of THF and cooled to less than 5° C. in an ice bath was added N-methyl-N-((2-isopropyl-4-thiazolyl)methyl)amine (3.78 g, 22.2 mmol) followed by a 5 mL THF rinse. A solution of N-phenoxycarbonyl-L-Valine (5.0 g, 21.1 mmol) in 20 mL of THF was added followed by a 5 mL THF rinse. Water (1.04 mL) was added, the cooling bath was removed, and the reaction was stirred at ambient temperature for 4.5 hours. Water (55 mL) was added, and the THF was removed under reduced pressure. Methyl tert-butyl ether (50 mL) was added, and as the solution stirred, the pH was adjusted to 9 with 4 N HCl. The aqueous phase was separated and washed with another 50 mL portion of MTBE. The aqueous product layer was stirred with 50 mL of toluene and adjusted to pH 3 with 4 N HCl. The aqueous layer was separated and extracted once more with toluene (50 mL). The combined toluene extracts were concentrated under reduced pressure. The residue obtained was redissolved in toluene, filtered, and rinsed with toluene. The combined filtrates were concentrated under reduced pressure. The product was crystallized from toluene-heptane (50 mLs of a 1:1 v/v solution), washed with heptane, and dried under vacuum to afford the title compound as a white powder.

Workup

  1. temperaturecooled to less than 5° C. in an ice bath
  2. washrinse
  3. washrinse
  4. additionWater (1.04 mL) was added
  5. customthe cooling bath was removed
  6. additionWater (55 mL) was added
  7. customthe THF was removed under reduced pressure
  8. additionMethyl tert-butyl ether (50 mL) was added
  9. stirringas the solution stirred
  10. customThe aqueous phase was separated
  11. washwashed with another 50 mL portion of MTBE
  12. stirringThe aqueous product layer was stirred with 50 mL of toluene
  13. customThe aqueous layer was separated
  14. extractionextracted once more with toluene (50 mL)
  15. concentrationThe combined toluene extracts were concentrated under reduced pressure
  16. customThe residue obtained
  17. filtrationfiltered
  18. washrinsed with toluene
  19. concentrationThe combined filtrates were concentrated under reduced pressure
  20. customThe product was crystallized from toluene-heptane (50 mLs of a 1:1 v/v solution),
  21. washwashed with heptane
  22. customdried under vacuum

Sources & evidence

ORD record
ord-7aac4e5dcc3248ba952912de5a810ba2
Source dataset
uspto-grants-2000_12
Patent number
US06160122

Reaction notes

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