1,3-Oxazolidine → 3-(5-tert-Butyloxazol-4-yl)-2-hydroxyacrylic acid

HRID 2074225Notes

Reaction equation

HRID 2074225 reaction equation
C([O:5][C:6]([C:8](NC(=O)OC(C)(C)C)=[CH:9][C:10]1[N:11]=[CH:12][O:13][C:14]=1[C:15]([CH3:18])([CH3:17])[CH3:16])=[O:7])(C)(C)C.[O:27]1CCNC1>C1COCC1>[C:15]([C:14]1[O:13][CH:12]=[N:11][C:10]=1[CH:9]=[C:8]([OH:27])[C:6]([OH:5])=[O:7])([CH3:18])([CH3:17])[CH3:16]

Participants

4

Reactant 2

HCID 5366831,3-OxazolidineHCID 72404735tert-Butyl 1-(tert-butoxycarbonyl)-2-(5-tert-butyloxazol-4-yl)vinylcarbamate

Product 1

HCID 665900433-(5-tert-Butyloxazol-4-yl)-2-hydroxyacrylic acidYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-40 °C

Procedure

To a solution of Ethyl 5-(tert-butyl)oxazole-4-carboxylate 2 (20 g, 101 mmol) in anhydrous THF (250 mL) was added LiAl (3.84 g, 101 mmol, Kanto Chemical, Tokyo, Japan, Cat. No. 24115-35) portionwise under argon atmosphere at −60° C., and the bath temperature was gradually increased up to −40° C. with stirring for 2 h. (In case that the temperature was more than −40° C., the reduction of the oxazole ring (oxazolidine formation) predominantly proceeded). After the reaction mixture was quenched with saturated NH4Cl aq (50 ml) at −60° C. (Please avoid rapid elevation of temperature. Some impurity increased.), AcOEt (250 ml) was-added and stirred for a few minutes, and the resulting precipitate was removed by celite filtration (Celite-535, Nacalai Tesque, Kyoto, Japan, Cat. No. 07509-05). The filtrate was washed with water (×2), 10% citric acid (×3, a byproduct, oxazolidine, can be removed by this separation) and saturated NaCl (×3), dried over anhydrous Na2SO4, and concentrated in vacuo to give an oil of corresponding oxazole alcohol 3 (10.6 g, 67%). Rf 0.50 (CHCl3:MeOH=10:0.5), 1H NMR (300 MHz CDCl3) δ 7.71 (s, 1H), 4.66 (s, 2H), 1.36 (s, 9H); HRMS(EI): m/z 155.0852 (M+) (Calcd for C8H13NO2: 155.0854). This oil was used to the next oxidation without further purification.

Workup

  1. customwas more than −40° C.
  2. customAfter the reaction mixture was quenched with saturated NH4Cl aq (50 ml) at −60° C. (
  3. temperatureSome impurity increased
  4. addition), AcOEt (250 ml) was-added
  5. stirringstirred for a few minutes
  6. customthe resulting precipitate was removed by celite filtration (Celite-535, Nacalai Tesque, Kyoto, Japan, Cat
  7. washThe filtrate was washed with water (×2), 10% citric acid (×3
  8. customa byproduct, oxazolidine, can be removed by this separation) and saturated NaCl (×3)
  9. dry with materialdried over anhydrous Na2SO4
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-15baee5400e14ad2b9aee2b6aaef0b82
Source dataset
uspto-grants-2011_04
Patent number
US07919497B2

Reaction notes

Loading…