Lithium Hydroxide → 5-{(1R)-1-[(tert-Butoxycarbonyl)amino]ethyl}-1,2-oxazole-3-carboxylic acid

HRID 2403143Notes

Reaction equation

HRID 2403143 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C:11]1[O:15][N:14]=[C:13]([C:16]([O:18]CC)=[O:17])[CH:12]=1)[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li+].[OH-]>C1COCC1>[C:1]([O:5][C:6]([NH:8][C@@H:9]([C:11]1[O:15][N:14]=[C:13]([C:16]([OH:18])=[O:17])[CH:12]=1)[CH3:10])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 59421477Ethyl 5-{(1R)-1-[(tert-butoxycarbonyl)amino]ethyl}-1,2-oxazole-3-carboxylate

Product 1

HCID 573555205-{(1R)-1-[(tert-Butoxycarbonyl)amino]ethyl}-1,2-oxazole-3-carboxylic acidYield 44.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (R)-tert-butyl but-3-yn-2-ylcarbamate (262.5 g, 1.56 mol) and (4-ethyl 2-chloro-2-(hydroxyimino)acetate (78.2 g, 0.52 mol) in DMF (1 L) was added dropwise Et3N (216 mL, 1.56 mol) at 90° C. The mixture was stirred for 5 hr, and then concentrated in vacuo. The residue was re-dissolved in ethyl acetate. The ethyl acetate solution was washed with water, dried over Na2SO4, and evaporated to provide the crude compound (R)-ethyl 5-(1-(tert-butoxycarbonylamino)ethyl)isoxazole-3-carboxylate. To a solution of (R)-ethyl 5-(1-(tert-butoxycarbonylamino)ethyl)isoxazole-3-carboxylate in THF (2 L) was added aqueous 2.5 N LiOH (1 L) at RT. The mixture was stirred for 1 hr, and then evaporated under reduced pressure to remove THF. The residue was partitioned between water (1 L) and ethyl acetate (0.5 L). The organic layer was separated and the aqueous layer was extracted with ethyl acetate twice. The aqueous layer was adjusted to pH 2 with 10% HCl and extracted with ethyl acetate (2×1 L). All the organic layers were combined, washed with water, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was dried under vacuum to give the crude product N.4, (R)-5-(1-(tert-butoxycarbonylamino)ethyl)isoxazole-3-carboxylic acid (55.2 g, 44.8%), which was used without further purification. 1H NMR (CDCl3) δ6.57 (s, 1H), 4.12 (q, 1H), 1.56 (d, 3H), 1.37 (s, 9H).

Workup

  1. customevaporated under reduced pressure
  2. customto remove THF
  3. customThe residue was partitioned between water (1 L) and ethyl acetate (0.5 L)
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with ethyl acetate twice
  6. extractionextracted with ethyl acetate (2×1 L)
  7. washwashed with water
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was dried under vacuum

Sources & evidence

ORD record
ord-9ba56665392848298a3d71c464a18161
Source dataset
uspto-grants-2014_08
Patent number
US08802657B2

Reaction notes

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