Dimethyl malonate → HCID 68734273, compound

HRID 387538Notes

Reaction equation

HRID 387538 reaction equation
[C:1]([O:8][CH3:9])(=[O:7])[CH2:2][C:3]([O:5][CH3:6])=[O:4].CCN(C(C)C)C(C)C.CO[CH:21]1[N:25]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C:24]([CH3:34])([CH3:33])[CH2:23][CH2:22]1.[NH4+].[Cl-]>C(Cl)Cl.Cl[Ti](Cl)(Cl)Cl>[C:29]([O:28][C:26]([N:25]1[C:24]([CH3:34])([CH3:33])[CH2:23][CH2:22][CH:21]1[CH:2]([C:1]([O:8][CH3:9])=[O:7])[C:3]([O:5][CH3:6])=[O:4])=[O:27])([CH3:32])([CH3:30])[CH3:31]

Participants

7

Reactant 4

HCID 7943Dimethyl malonateHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 59564912HCID 59564912, compound

Product 1

HCID 68734273HCID 68734273, compoundYield 75.9%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent4×

Procedure

TiCl4 (1.9 mL, 1.9 mmol) as a 1M DCM solution was added to a solution of dimethyl malonate (0.195 mL, 1.70 mmol) in DCM (10 mL) at 0° C. under N2, and the reaction was stirred for 10 minutes. DIEA (0.3 mL, 1.7 mmol) was then added slowly, and the reaction was stirred for an additional 30 minutes at 0° C. A DCM (2 mL) solution of tert-butyl 5-methoxy-2,2-dimethylpyrrolidine-1-carboxylate (325 mg, 1.4 mmol) was then slowly added dropwise, and the reaction was stirred at 0° C. for 10 minutes. Saturated NH4Cl was then added, and then reaction was diluted with DCM and washed with saturated NaHCO3. The organic fractions were then dried, filtered, and concentrated to give the crude product, which was purified by column chromatography (500:50-500:90 hexanes:EtOAc) to give dimethyl 2-(1-(tert-butoxycarbonyl)-5,5-dimethylpyrrolidin-2-yl)malonate (0.35 g, 75%).

Workup

  1. stirringthe reaction was stirred for an additional 30 minutes at 0° C
  2. stirringthe reaction was stirred at 0° C. for 10 minutes
  3. customreaction
  4. washwashed with saturated NaHCO3
  5. customThe organic fractions were then dried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give the crude product, which
  9. customwas purified by column chromatography (500:50-500:90 hexanes:EtOAc)

Sources & evidence

ORD record
ord-d9be5ff4f15f4702be1c50661b5df228
Source dataset
uspto-grants-2013_02
Patent number
US08372842B2

Reaction notes

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