Sodium hydride → Ureidovaline

HRID 1275349Notes

Reaction equation

HRID 1275349 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>C1COCC1>[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

5

Reactant 3

HCID 24758Sodium hydride2×HCID 9816135N-Phenoxycarbonyl-L-valineHCID 107496872-Isopropyl-4-(N-methyl)amino-methyl thiazole

Product 1

HCID 9818282UreidovalineYield 24%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirred slurry of 60% oil dispersion NaH (200 mg, 5 mmol) at <5° C. in 10 mL of THF was added N-phenoxycarbonyl-L-Valine (1.0 g, 4.2 mmol) followed by a 10 mL THF rinse and keeping the temperature <5° C. using an ice-water bath. In another flask, N-methyl-N-((2-isopropyl-4-thiazolyl)methyl)amine (851 mg, 5 mmol) was added to a <5° C. slurry of 60% oil dispersion NaH (220 mg, 5.5 mmol) in 10 mL of THF maintaining the temperature <5° C. Both solutions were stirred for 15 minutes, and then the acid salt solution was added to the amine salt solution in one portion. The reaction was allowed to proceed at <10° C. for 1 hour and then at ambient temperature for 30 minutes. The reaction was quenched by the addition of 10 mL of MeOH, and the reaction mixture was then concentrated in vacuo. The resulting residue was dissolved in a minimum of EtOAc and flash chromatographed on silica gel eluting with 1:1 ethyl acetate in isopropanol. The residue obtained was further purified by preparative thin layer chromatography eluting with 33.6% CHCl3, 7.7% H2O, 3.5% HOAc, 25.2% MeOH and 30% EtOAc to afford the title compound (310 mg, 24%) as a yellow oil.

Workup

  1. washrinse
  2. customthe temperature <5° C.
  3. waitto proceed at <10° C. for 1 hour
  4. waitat ambient temperature for 30 minutes
  5. customThe reaction was quenched by the addition of 10 mL of MeOH
  6. concentrationthe reaction mixture was then concentrated in vacuo
  7. dissolutionThe resulting residue was dissolved in a minimum of EtOAc and flash
  8. customchromatographed on silica gel eluting with 1:1 ethyl acetate in isopropanol
  9. customThe residue obtained
  10. customwas further purified by preparative thin layer chromatography
  11. washeluting with 33.6% CHCl3, 7.7% H2O, 3.5% HOAc, 25.2% MeOH and 30% EtOAc

Sources & evidence

ORD record
ord-3600fbb879da4d34961f0b8337f29ffa
Source dataset
uspto-grants-2000_12
Patent number
US06160122

Reaction notes

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