2,6-Dimethoxybenzaldehyde → Ethyl 2-(2,6-dimethoxyphenyl)-4,5-dioxo-1-(4-(trifluoromethoxy)-benzyl)pyrrolidine-3-carboxylate

HRID 594396Notes

Reaction equation

HRID 594396 reaction equation
[F:1][C:2]([F:13])([F:12])[O:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][NH2:11])=[CH:6][CH:5]=1.[CH3:14][O:15][C:16]1[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[C:17]=1[CH:18]=O.[Na].[C:27]([O:37][CH2:38][CH3:39])(=[O:36])[CH2:28][C:29]([C:31](OCC)=[O:32])=[O:30]>CCO>[CH3:14][O:15][C:16]1[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[C:17]=1[CH:18]1[CH:28]([C:27]([O:37][CH2:38][CH3:39])=[O:36])[C:29](=[O:30])[C:31](=[O:32])[N:11]1[CH2:10][C:7]1[CH:6]=[CH:5][C:4]([O:3][C:2]([F:12])([F:13])[F:1])=[CH:9][CH:8]=1

Participants

5

Reactant 3

HCID 964042,6-DimethoxybenzaldehydeHCID 5718464-(Trifluoromethoxy)benzylamineHCID 57351814Diethyl 2-oxosuccinate,sodium salt

Product 1

HCID 69082391Ethyl 2-(2,6-dimethoxyphenyl)-4,5-dioxo-1-(4-(trifluoromethoxy)-benzyl)pyrrolidine-3-carboxylate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of commercially available (4-(trifluoromethoxy)phenyl)methanamine (11.858 g; 60.17 mmol) and commercially available 2,6-dimethoxybenzaldehyde (10.000 g; 60.17 mmol) in anh. EtOH (160 ml) was treated with diethyl oxalacetate sodium salt (13.312 g; 60.17 mmol). The resulting mixture was then refluxed, under nitrogen, for 8 h. After cooling to rt, the reaction mixture was concentrated to dryness under reduced pressure. DCM was added and the resulting heterogeneous mixture was washed with 1 M aq. HCl (2×), and with brine. The separated organic layer was then dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM to DCM/MeOH=30/1) afforded ethyl 2-(2,6-dimethoxyphenyl)-4,5-dioxo-1-(4-(trifluoromethoxy)benzyl)pyrrolidine-3-carboxylate as an orange oil. LC-MS (conditions A): tR=0.89 min.; [M+H]+: 481.92 g/mol.

Workup

  1. temperatureThe resulting mixture was then refluxed, under nitrogen, for 8 h
  2. concentrationthe reaction mixture was concentrated to dryness under reduced pressure
  3. additionDCM was added
  4. washthe resulting heterogeneous mixture was washed with 1 M aq. HCl (2×)
  5. dry with materialThe separated organic layer was then dried over anh. MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure
  8. customPurification by FC (DCM to DCM/MeOH=30/1)

Sources & evidence

ORD record
ord-f97dd8c928a845c29c2a0b2de63cca41
Source dataset
uspto-grants-2016_01
Patent number
US09242970B2

Reaction notes

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