Triethylamine → Ethyl 5-{(1R)-1-[(tert-butoxycarbonyl)amino]ethyl}-1,2-oxazole-3-carboxylate

HRID 2066909Notes

Reaction equation

HRID 2066909 reaction equation
[CH3:1][C@@H:2]([NH:5][C:6](=[O:12])[O:7][C:8]([CH3:11])([CH3:10])[CH3:9])[C:3]#[CH:4].Cl/[C:14](=[N:20]\[OH:21])/[C:15]([O:17][CH2:18][CH3:19])=[O:16].CCN(CC)CC>CN(C=O)C>[C:8]([O:7][C:6]([NH:5][C@@H:2]([C:3]1[O:21][N:20]=[C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:4]=1)[CH3:1])=[O:12])([CH3:11])([CH3:10])[CH3:9]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 95760052-Chloro-2-hydroxyiminoacetic acid ethyl esterHCID 45092359tert-Butyl (2R)-but-3-yn-2-ylcarbamate

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of (R)-tert-butyl but-3-yn-2-ylcarbamate (262.5 g, 1.56 mol) and (Z)-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) δ 6.57 (s, 1H), 4.12 (q, 1H), 1.56 (d, 3 H), 1.37 (s, 9H).

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was re-dissolved in ethyl acetate
  3. washThe ethyl acetate solution was washed with water
  4. dry with materialdried over Na2SO4
  5. customevaporated

Sources & evidence

ORD record
ord-c7814e761bf24a61860f6567eb8631e5
Source dataset
uspto-grants-2012_10
Patent number
US08293752B2

Reaction notes

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