Hydrochloric Acid → Ureidovaline

HRID 1275352Notes

Reaction equation

HRID 1275352 reaction equation
[H-].[Na+].O([C:10]([NH:12][C@H:13]([C:17]([OH:19])=[O:18])[CH:14]([CH3:16])[CH3:15])=[O:11])C1C=CC=CC=1.[CH3:20][NH:21][CH2:22][C:23]1[N:24]=[C:25]([CH:28]([CH3:30])[CH3:29])[S:26][CH:27]=1.Cl.[OH-].[Na+]>C1COCC1.O>[CH3:20][N:21]([C:10]([NH:12][C@H:13]([C:17]([OH:19])=[O:18])[CH:14]([CH3:15])[CH3:16])=[O:11])[CH2:22][C:23]1[N:24]=[C:25]([CH:28]([CH3:30])[CH3:29])[S:26][CH:27]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 9816135N-Phenoxycarbonyl-L-valineHCID 107496872-Isopropyl-4-(N-methyl)amino-methyl thiazole

Product 1

HCID 9818282Ureidovaline

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirred slurry of 95% NaH (355 mg, 14.1 mmol) at -5° C. in 15 mL of THF was added a solution of N-phenoxycarbonyl-L-Valine (2.99 g, 12.6 mmol) and N-methyl-N-((2-isopropyl-4-thiazolyl)methyl)amine (2.16 g, 12.7 mmol) in 15 mL of THF followed by a 5 mL THF rinse. The reaction mixture was stirred at or below 0° C. for three hours and then allowed to warm to ambient temperature. After two days at ambient temperature, the THF was removed under reduced pressure. The remaining aqueous residue was added to 31 mL of methyl tert-butyl ether and treated with stirring with a solution of 0.15 mL (1.8 mmol) of concentrated hydrochloric acid in 30 mL of water. The pH of the solution was adjusted to ~9 with 10% sodium hydroxide solution. The aqueous phase was washed with 30 mL of methyl tert-butyl ether. The aqueous phase was treated with 30 mL of toluene and acidified to pH 3 with 4 N HCl. The aqueous layer was separated and extracted with an additional 30 mL aliquot of toluene. The combined toluene extracts were concentrated under reduced pressure. The title compound was crystallized from toluene-heptane as a crystalline solid (3.32 g, 84%). m.p. 82.8-93.8° C. 1H NMR (CDCl3, 400 MHz) δ 1.02 (d, 3H), 1.04 (d, 3H), 1.38 (d, 6H), 2.30 (m, 1H), 2.30 (m, 1H), 3.00 (s, 3H), 3.28 (m, 1H), 4.24 (dd, 1H), 4.48 (AB quartet, 2H), 6.10-6.14 (br s, 1H), 7.02 (s, 1H). 13C NMR (CDCl3, 400 MHz) δ 18.1, 19.5, 23.0, 23.1, 29.9, 33.1, 34.9, 49.2, 59.6, 114.4, 149.4, 151.5, 159.8, 174.9. IR (film) 3200-3400, 1730,1620 cm-1. High Resolution MS Calc for C14H23N3SO3 : (FAB) m/e 314.1538 (M+H)+. Found: 314.1530.

Workup

  1. washrinse
  2. waitAfter two days at ambient temperature
  3. customthe THF was removed under reduced pressure
  4. additionThe remaining aqueous residue was added to 31 mL of methyl tert-butyl ether
  5. additiontreated
  6. washThe aqueous phase was washed with 30 mL of methyl tert-butyl ether
  7. additionThe aqueous phase was treated with 30 mL of toluene
  8. customThe aqueous layer was separated
  9. extractionextracted with an additional 30 mL aliquot of toluene
  10. concentrationThe combined toluene extracts were concentrated under reduced pressure
  11. customThe title compound was crystallized from toluene-heptane as a crystalline solid (3.32 g, 84%)

Sources & evidence

ORD record
ord-bef53342fa38493abae1aea87567e71b
Source dataset
uspto-grants-2000_12
Patent number
US06160122

Reaction notes

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