4-Oxo-7,8-dihydro-4H-cyclohepta[b]pyrrole-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester → 6-Methyl-4-oxo-5,6,7,8-tetrahydro-4H-cyclohepta[b]pyrrole-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester

HRID 982883Notes

Reaction equation

HRID 982883 reaction equation
[Li][CH3:2].[CH2:3]([O:5][C:6]([C:8]1[C:9]2[C:24](=[O:25])[CH:23]=[CH:22][CH2:21][CH2:20][C:10]=2[N:11]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH:12]=1)=[O:7])[CH3:4]>CCOCC.C1COCC1.[Cu]I>[CH2:3]([O:5][C:6]([C:8]1[C:9]2[C:24](=[O:25])[CH2:23][CH:22]([CH3:2])[CH2:21][CH2:20][C:10]=2[N:11]([C:13]([O:15][C:16]([CH3:19])([CH3:17])[CH3:18])=[O:14])[CH:12]=1)=[O:7])[CH3:4]

Participants

6

Reactant 2

HCID 207622234-Oxo-7,8-dihydro-4H-cyclohepta[b]pyrrole-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl esterHCID 178418348HCID 178418348, compound

Product 1

HCID 207622226-Methyl-4-oxo-5,6,7,8-tetrahydro-4H-cyclohepta[b]pyrrole-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

MeLi (1.4M in ether, 2 ml) is added dropwise to a stirred suspension of CuI (268 mg, 1.40 mmol) in Et2O at 0° C. The reaction mixture is kept at 0° C. for 15 min. 4-oxo-7,8-dihydro-4H-cyclohepta[b]pyrrole-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester (300 mg, 0.94 mmol) in THF is added slowly to the solution at 0° C., the reaction mixture is allowed to warm up to room temperature over a period of 30 min and then quenched with saturated NH4Cl(aq., 30 ml). 50 ml Et2O is added and stirring is continued for 5 min. The layers are separated; the organic layer is washed with water (20 ml), dried (Na2SO4), and evaporated. Flash chromatography (30% EtOAc/hexanes) provides the title compound as white powder. 1H NMR (400 MHz, CDCl3) δ 1.02 (3H, d), 1.28 (3H, t), 1.56 (9H+1H, s+m), 1.92 (1H, m), 2.15 (1H, m), 2.48 (1H, q), 2.80 (1H, q), 3.15-3.25 (2H, m), 4.24 (2H, q), 7.57 (1H, s). MS (ES+) 336 (M+1) Step 2: 6-Methyl-4-oxo-1,4,5,6,7,8-hexahydro-cyclohepta[b]pyrrole-3-carboxylic acid ethyl ester

Workup

  1. customquenched with saturated NH4Cl(aq., 30 ml)
  2. addition50 ml Et2O is added
  3. waitis continued for 5 min
  4. customThe layers are separated
  5. washthe organic layer is washed with water (20 ml)
  6. dry with materialdried (Na2SO4)
  7. customevaporated

Sources & evidence

ORD record
ord-56b1a1bfce4b4dd7b9794dd0604d4e5d
Source dataset
uspto-grants-2005_03
Patent number
US06861529B2

Reaction notes

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