Iodoethane → HCID 57758661, compound

HRID 229514Notes

Reaction equation

HRID 229514 reaction equation
[CH3:1][C:2]1([C:16]([O:18][CH3:19])=[O:17])[CH2:6][C:5](=[O:7])[N:4]([C@@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH3:9])[CH2:3]1.[CH:20]([N-]C(C)C)(C)[CH3:21].[Li+].C(C1C=CC=CC=1)C.C(I)C>O1CCCC1.CCCCCCC.CN(C)P(=O)(N(C)C)N(C)C>[CH2:20]([CH:6]1[C:5](=[O:7])[N:4]([C@@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH3:9])[CH2:3][C:2]1([C:16]([O:18][CH3:19])=[O:17])[CH3:1])[CH3:21]

Participants

8

Reactant 4

HCID 6340IodoethaneHCID 7500EthylbenzeneHCID 2724682Lithium diisopropylamideHCID 10061206HCID 10061206, compound

Product 1

HCID 57758661HCID 57758661, compound

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8900HeptaneSolventHCID 12679HexamethylphosphoramideSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of the methyl 3-methyl-5-oxo-1-[(R)-1-phenylethyl]pyrrolidin-3-yl-carboxylate (stereoisomer A) produced in Reference Example 31 (19.86 g, 76.0 mmol) and hexamethylphosphoric triamide (30 mL) in tetrahydrofuran (300 mL), a solution of lithium diisopropyl amide in heptane, tetrahydrofuran, and ethylbenzene (1.8M, 63.3 mL, 113.9 mmol) was gradually added in 15 minutes at −78° C. After stirring the mixture at −78° C. for 30 minutes, ethyl iodide (12.2 mL, 152.0 mmol) was added dropwise at the same temperature in 10 minutes. After stirring at −78° C. for 1 hour, the mixture was quenched by adding saturated aqueous solution of ammonium chloride (100 mL). The reaction mixture was extracted with ethyl acetate (300 mL), and the organic layer was washed with water (200 mL×2) and saturated aqueous solution of sodium chloride (200 mL). After drying with anhydrous sodium sulfate, the dessicating agent was removed by filtration, and the solvent was removed by distillation under reduced pressure. The resulting crude product was purified by silica gel column chromatography (hexane:ethyl acetate, 90:10→85:15→80:20) to obtain 10.63 g of the title compound (a mixture of stereoisomers of position 4, 36.7 mmol, 48%) as a pale yellow oil.

Workup

  1. stirringAfter stirring at −78° C. for 1 hour
  2. customthe mixture was quenched
  3. additionby adding saturated aqueous solution of ammonium chloride (100 mL)
  4. extractionThe reaction mixture was extracted with ethyl acetate (300 mL)
  5. washthe organic layer was washed with water (200 mL×2) and saturated aqueous solution of sodium chloride (200 mL)
  6. dry with materialAfter drying with anhydrous sodium sulfate
  7. customthe dessicating agent was removed by filtration
  8. customthe solvent was removed by distillation under reduced pressure
  9. customThe resulting crude product was purified by silica gel column chromatography (hexane:ethyl acetate, 90:10→85:15→80:20)

Sources & evidence

ORD record
ord-48352b2735134523a7cb6efcccd7a362
Source dataset
uspto-grants-2009_07
Patent number
US07563805B2

Reaction notes

Loading…