Lithium Bromide → 1-Acetyl-6'-benzyl-1',2'-dihydrospiro[azetidine-3,3'-indole]-1'-yl-carboxylic acid tert-butyl ester

HRID 1475344Notes

Reaction equation

HRID 1475344 reaction equation
[Li+].[Br-].[C:3]([O:7][C:8]([N:10]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16](Cl)[CH:17]=2)[C:12]2([CH2:22][N:21]([C:23](=[O:25])[CH3:24])[CH2:20]2)[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].[Br-].[CH2:27]([Zn+])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>CN1C(=O)CCC1.C(N1C=CN(C(C)C)C1=[Pd-3](Cl)(Cl)C1C(Cl)=CC=CN=1)(C)C>[C:3]([O:7][C:8]([N:10]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH:17]=2)[C:12]2([CH2:22][N:21]([C:23](=[O:25])[CH3:24])[CH2:20]2)[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4]

Participants

6

Reactant 3

HCID 82050Lithium BromideHCID 867239611-Acetyl-6'-chloro-1',2'-dihydrospiro[azetidine-3,3'-indole]-1'-yl-carboxylic acid tert-butyl esterHCID 178419772HCID 178419772, compound2×

Product 1

HCID 867239601-Acetyl-6'-benzyl-1',2'-dihydrospiro[azetidine-3,3'-indole]-1'-yl-carboxylic acid tert-butyl esterYield 175.7%

Reagents, catalysts & solvents 2

HCID 178456358HCID 178456358, compoundCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

(1,3-Diisopropylimidazol-2-ylidene)(3-chloropyridyl)palladium (II) dichloride (2 mg, 10 mol %) and LiBr (41 mg, 0.47 mmol) were dissolved in dry NMP and the solution was degassed with N2 for 5 minutes. Then 1-acetyl-6′-chloro-1′,2′-dihydrospiro[azetidine-3,3′-indole]-1′-yl-carboxylic acid tert-butyl ester (100 mg, 0.29 mmol) and benzylzinc bromide (0.5M solution in toluene, 950 μL, 0.475 mmol) were added. The reaction mixture was stirred under N2 for 4 h. A second aliquot of catalyst (2 mg) and benzylzinc bromide (950 μL) were added and stirring maintained for 4 h. The reaction was quenched with water and extracted with EtOAc. The organic phase was dried (MgSO4), filtered and concentrated. The crude material was purified by column chromatography (EtOAc:petrol 1:1 to EtOAc 100%) to give the title compound (200 mg) as a pale yellow oil (ca. 50% pure by NMR, contaminated with NMP), used without further purification. MS: [M+H]+=393.

Workup

  1. customthe solution was degassed with N2 for 5 minutes
  2. stirringstirring
  3. temperaturemaintained for 4 h
  4. customThe reaction was quenched with water
  5. extractionextracted with EtOAc
  6. dry with materialThe organic phase was dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material was purified by column chromatography (EtOAc:petrol 1:1 to EtOAc 100%)

Sources & evidence

ORD record
ord-d8dc1555e6a2438ca826c3184a5b16f6
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

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