Lithium hydroxide, monohydrate → HCID 68952635, compound

HRID 2039948Notes

Reaction equation

HRID 2039948 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][C:5]1([C:20]([O:22]C)=[O:21])[C:18](=[O:19])[N:8]2[C@@H:9]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[O:10][CH2:11][C@@H:7]2[CH2:6]1.O[Li].O>C1COCC1.O>[Cl:1][CH2:2][CH2:3][CH2:4][C:5]1([C:20]([OH:22])=[O:21])[C:18](=[O:19])[N:8]2[C@@H:9]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)[O:10][CH2:11][C@@H:7]2[CH2:6]1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 580114951H,3H-Pyrrolo[1,2-c]oxazole-6-carboxylic acid,6-(3-chloropropyl)tetrahydro-5-oxo-3-phenyl-,methyl ester,(3R,7aS)-

Product 1

HCID 68952635HCID 68952635, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

The (3R,7aS)-methyl 6-(3-chloropropyl)-5-oxo-3-phenyl-hexahydropyrrolo[1,2-c]oxazole-6-carboxylate (36.90 g) was dissolved in 300 mL of THF and the mixture cooled to 0° C. A solution of LiOH.H2O (22.97 g, 0.548 mol, 5.0 equiv) in water (273 mL, 2.0 M) was cooled to ˜5° C. and added to the THF solution. The mixture was stirred at 10° C. and the progress of the hydrolysis monitored by LC/MS. After 3 h the methyl ester was completely consumed. EtOAc (100 mL) was added and concentrated HCL added till the pH<2. The mixture was transferred to a separatory funnel and the layers separated. The aqueous layer was extracted with 100 mL EtOAc, the combined organic layers washed with brine, dried over Na2SO4, filtered and evaporated. The (3R,7aS)-6-(3-chloropropyl)-5-oxo-3-phenyl-hexahydropyrrolo[1,2-c]oxazole-6-carboxylic acid was isolated as a tan solid (32.65 g, 92% yield) after removal of residual solvent in vacuo.

Workup

  1. customAfter 3 h the methyl ester was completely consumed
  2. additionEtOAc (100 mL) was added
  3. concentrationconcentrated HCL
  4. additionadded till the pH<2
  5. customThe mixture was transferred to a separatory funnel
  6. customthe layers separated
  7. extractionThe aqueous layer was extracted with 100 mL EtOAc
  8. washthe combined organic layers washed with brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. customevaporated

Sources & evidence

ORD record
ord-45b67390324d49569f63d52dc06c31fa
Source dataset
uspto-grants-2013_11
Patent number
US08580823B2

Reaction notes

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