Dichloromethane → Methyl(6S)-2'-oxo-1'-{[2-(trimethylsilyl)ethoxy]methyl}-1',2',5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridine]-3-carboxylate

HRID 406526Notes

Reaction equation

HRID 406526 reaction equation
Br[C:2]1[CH:3]=[C:4]2[CH2:27][C:9]3([C:17]4[C:12](=[N:13][CH:14]=[CH:15][CH:16]=4)[N:11]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:10]3=[O:26])[CH2:8][C:5]2=[N:6][CH:7]=1.[CH2:28](Cl)Cl.[C:31]([O-:34])(=[O:33])C.[Na+].[C]=O>CO.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[O:26]=[C:10]1[N:11]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:12]2=[N:13][CH:14]=[CH:15][CH:16]=[C:17]2[C@@:9]21[CH2:8][C:5]1=[N:6][CH:7]=[C:2]([C:31]([O:34][CH3:28])=[O:33])[CH:3]=[C:4]1[CH2:27]2

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 517045Sodium AcetateHCID 68749705HCID 68749705, compoundHCID 178418416HCID 178418416, compound

Product 1

HCID 86665189Methyl(6S)-2'-oxo-1'-{[2-(trimethylsilyl)ethoxy]methyl}-1',2',5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridine]-3-carboxylate

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 887MethanolSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 3-bromo-1′-{[2-(trimethylsilyl)ethoxy]methyl}-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (22.0 g, 49.3 mmol), PdCl2(dppf).CH2Cl2 (2.012 g, 2.46 mmol), and sodium acetate (8.1 g, 99 mmol) in in methanol (150 mL) was pressurized to 300 psi of carbon monoxide and then heated at 85° C. for 72 h. The reaction mixture was allowed to cool then concentrated. The residue was purified via silica gel chromatography (heptane initially, grading to 100% EtOAc) to give the title compound as a racemic mixture. MS: m/z=426.1 (M+1). Resolution of the enantiomers by supercritical fluid chromatography (SFC) using a ChiralPak® AD-H column and eluting with 40% ethanol in CO2 (0.05% diethylamine as modifier) provided the title compound as the second enantiomer to elute.

Workup

  1. temperatureto cool
  2. concentrationthen concentrated
  3. customThe residue was purified via silica gel chromatography (heptane initially

Sources & evidence

ORD record
ord-ad762160378f44d6a72bb6e395e74c75
Source dataset
uspto-grants-2014_06
Patent number
US08754096B2

Reaction notes

Loading…