Diethyl Ether → HCID 11545724, compound

HRID 2223772Notes

Reaction equation

HRID 2223772 reaction equation
[C:1]([Cu])#N.[Li]C.CCOCC.FC(F)(F)S(O[C:17]1[C:24]2([CH2:25][C:26]3[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[CH:28][CH:27]=3)[N:20]([CH2:21][CH2:22][CH2:23]2)[C:19](=[O:34])[C:18]=1[C:35]1[CH:40]=[C:39]([Cl:41])[CH:38]=[C:37]([Cl:42])[CH:36]=1)(=O)=O.[NH4+].[OH-]>C1COCC1>[Cl:42][C:37]1[CH:36]=[C:35]([C:18]2[C:19](=[O:34])[N:20]3[C:24]([CH2:25][C:26]4[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[CH:28][CH:27]=4)([C:17]=2[CH3:1])[CH2:23][CH2:22][CH2:21]3)[CH:40]=[C:39]([Cl:41])[CH:38]=1

Participants

7

Reactant 5

HCID 3283Diethyl EtherHCID 14923Ammonium HydroxideHCID 86603584HCID 86603584, compoundHCID 178418348HCID 178418348, compoundHCID 178418546HCID 178418546, compound

Product 1

HCID 11545724HCID 11545724, compoundYield 14%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of CuCN (22.5 mg, 0.25 mmol) in dry THF (2 ML) at −78° C., under nitrogen atmosphere, was added a solution of MeLi in Et2O (1.4 M, 0.37 mL, 0.5 mmol). The mixture was stirred for 30 min and treated drop wise with a solution of 7a-(4-cyanobenzyl)-6-(3,5-dichlorophenyl)-5-oxo-2,3,5,7a-tetrahydro-1H-pyrrolizin-7-yl trifluoromethanesulfonate 26 (50 mg, 0.09 mmol) in THF (1 mL). The reaction was stirred for 2 h at −78° C. and 20 min. at −20° C. The reaction was treated with 10% aqueous NH4OH (10 ml), stirred at rt. for 10 min. and extracted with Et2O (4×10 mL). The extracts were combined sat. NaCl solution (10 ml), dried (MgSO4) and solvent removed. The resulting oil was purified using preparative HPLC to give 4-{[6-(3,5-Dichlorophenyl)-7-methyl-5-oxo-2,3-dihydro-1H-pyrrolizin-7a(5H)-yl]methyl}benzonitrile IX (5 mg, 14%), LCMS (m/z) 397/399 (M++H), HPLC Retention Time/Condition 1: 1.86 min.

Workup

  1. stirringThe reaction was stirred for 2 h at −78° C. and 20 min. at −20° C
  2. stirringstirred at rt
  3. waitfor 10 min.
  4. extractionextracted with Et2O (4×10 mL)
  5. dry with materialdried (MgSO4) and solvent
  6. customremoved
  7. customThe resulting oil was purified

Sources & evidence

ORD record
ord-099344f2c7a54059b6324e8c0d9559a1
Source dataset
uspto-grants-2008_05
Patent number
US07375237B2

Reaction notes

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