Methyl iodide → HCID 66773582, compound

HRID 1644812Notes

Reaction equation

HRID 1644812 reaction equation
[CH:1](NC(C)C)(C)C.[Li]CCCC.[Li+].CC([N-]C(C)C)C.[C:21]([O:25][C:26]([N:28]1[CH2:32][CH:31]([O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH2:30][C@@H:29]1[C:41]([OH:43])=[O:42])=[O:27])([CH3:24])([CH3:23])[CH3:22].CI>C1COCC1>[C:21]([O:25][C:26]([N:28]1[CH2:32][CH:31]([O:33][CH2:34][C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH2:30][C:29]1([CH3:1])[C:41]([OH:43])=[O:42])=[O:27])([CH3:24])([CH3:22])[CH3:23]

Participants

7

Reactant 5

HCID 6328Methyl iodideHCID 7912DiisopropylamineHCID 2724682Lithium diisopropylamideHCID 66775084HCID 66775084, compoundHCID 178418339Butyllithium

Product 1

HCID 66773582HCID 66773582, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a cooled (−78° C.) solution of diisopropylamine (0.032 mol) in dry THF (15 mL), n-BuLi (0.030 mol) was added dropwise under argon atmosphere, and the reaction was stirred for 30 min at −78° C., then for one hour at −20° C. The resulting LDA solution was transferred to the solution of the known compound (R)-4-benzyloxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (CAS: 54631-81-1, e.g. Tetrahedron, 42(21), 6039-45; 1986) (3.5 g, 0.011 mol) in THF (15 mL) at −78° C., and the mixture was stirred for 30 minutes at −78° C., then at 0° C. for one hour. The reaction mixture was once again cooled to −78° C. and methyl iodide (0.82 mL, 0.013 mol) was added to it over 10 min and stirred the reaction mixture was stirred at 0° C. then at rt for one hour. After completion of the reaction by TLC, the reaction mixture was quenched with 1N HCl (20 mL) and extracted with DCM. The organic layer was concentrated under reduced pressure to give a crude material, which was purified through column chromatography (10-20% ethyl acetate:hexane, basic alumina, diameter of column—2.5 cm, height of alumina—approx. 7 inch) to afford the desired (rac)-4-benzyloxy-2-methyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 800 mg (22%) as a white solid.

Workup

  1. additionwas added dropwise under argon atmosphere
  2. waitfor one hour at −20° C
  3. stirringthe mixture was stirred for 30 minutes at −78° C.
  4. waitat 0° C. for one hour
  5. temperatureThe reaction mixture was once again cooled to −78° C.
  6. stirringstirred the reaction mixture
  7. stirringwas stirred at 0° C.
  8. waitat rt for one hour
  9. customAfter completion of the reaction by TLC
  10. customthe reaction mixture was quenched with 1N HCl (20 mL)
  11. extractionextracted with DCM
  12. concentrationThe organic layer was concentrated under reduced pressure
  13. customto give a crude material, which
  14. customwas purified through column chromatography (10-20% ethyl acetate:hexane, basic alumina, diameter of column—2.5 cm, height of alumina—approx. 7 inch)

Sources & evidence

ORD record
ord-7c9209b4bbf045739bd24e74a46aca3c
Source dataset
uspto-grants-2012_02
Patent number
US08124636B2

Reaction notes

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