Acetic Anhydride → HCID 11659251, compound

HRID 1527314Notes

Reaction equation

HRID 1527314 reaction equation
[CH3:1][O:2][C:3]([C@@H:5]1[CH2:9][CH2:8][C:7](=[O:10])[N:6]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:4].[C:18](OC(=O)C)(=[O:20])[CH3:19].CCN(CC)CC>C1COCC1.C1(C)C=CC=CC=1.CN(C)C1C=CN=CC=1>[CH3:1][O:2][C:3]([C@@H:5]1[CH2:9][CH2:8][CH:7]([O:10][C:18](=[O:20])[CH3:19])[N:6]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:4]

Participants

7

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 108684851-O-tert-butyl 2-O-methyl (2S)-5-oxopyrrolidine-1,2-dicarboxylate

Product 1

HCID 11659251HCID 11659251, compound

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of (S)-5-oxo-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (prepared according to J. Org. Chem. 2003, 60, 7219) (1.9 g, 7.8 mmol) in THF (25 mL), cooled to −78° C., was slowly added DibalH (1 M in toluene; 11.0 mL, 11.0 mmol) under an argon atmosphere, followed by stirring of the solution at −78° C. for 1 h. The reaction was quenched by addition of a saturated aqueous solution of NH4Cl (30 mL). The mixture was allowed to warm up to RT, and a 10% aqueous Na2CO3 solution (20 mL) and CH2Cl2 (70 mL) were subsequently added. The layers were separated and the aqueous phase was extracted with CH2Cl2 (2×50 mL). The combined organics were dried (Na2SO4) and concentrated in vacuo. The residue was dissolved in CH2Cl2 (25 mL), acetic anhydride (2.21 mL, 23.4 mmol), NEt3 (3.26 mL, 23.4 mmol) and 4-dimethylaminopyridine (0.2 g, 1.6 mmol) were subsequently added and the reaction mixture was stirred at RT overnight. The organics were washed with a saturated aqueous NaHCO3 solution (10 mL) and 1M aqueous HCl, dried (Phase separator) and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (c-hexane/EtOAc gradient 3:1 to 1:1) to give the title compound. TLC, Rf (c-hexane/EtOAc 1:1)=0.5; MS: 310.0 [M+Na]+, 597.3 [2M+Na]+.

Workup

  1. customThe reaction was quenched by addition of a saturated aqueous solution of NH4Cl (30 mL)
  2. temperatureto warm up to RT
  3. additiona 10% aqueous Na2CO3 solution (20 mL) and CH2Cl2 (70 mL) were subsequently added
  4. customThe layers were separated
  5. extractionthe aqueous phase was extracted with CH2Cl2 (2×50 mL)
  6. dry with materialThe combined organics were dried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. dissolutionThe residue was dissolved in CH2Cl2 (25 mL)
  9. stirringthe reaction mixture was stirred at RT overnight
  10. washThe organics were washed with a saturated aqueous NaHCO3 solution (10 mL) and 1M aqueous HCl
  11. customdried (Phase separator)
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified by flash column chromatography on silica gel (c-hexane/EtOAc gradient 3:1 to 1:1)

Sources & evidence

ORD record
ord-c76fbf038a0d4c8d8788feefb14a073d
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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