Dichloromethane → HCID 136377183, compound

HRID 1027303Notes

Reaction equation

HRID 1027303 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([N:8]2[CH2:12][C@@H:11]3[CH2:13][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15][C@@H:10]3[CH2:9]2)=[CH:4][CH:3]=1.[Cl:23][C:24]1[CH:25]=[CH:26][C:27](B2OC(C)(C)C(C)(C)O2)=[C:28]([OH:30])[CH:29]=1.C(=O)([O-])[O-].[Na+].[Na+].C(Cl)Cl>O1CCOCC1.O.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]>[Cl:23][C:24]1[CH:25]=[CH:26][C:27]([C:2]2[N:7]=[N:6][C:5]([N:8]3[CH2:12][C@@H:11]4[CH2:13][N:14]([C:16]([O:18][C:19]([CH3:21])([CH3:20])[CH3:22])=[O:17])[CH2:15][C@@H:10]4[CH2:9]3)=[CH:4][CH:3]=2)=[C:28]([OH:30])[CH:29]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 44190436HCID 44190436, compoundHCID 676093145-Chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol

Product 1

HCID 136377183HCID 136377183, compoundYield 43.2%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

The reaction mixture of (3aR,6aS)-tert-butyl 5-(6-chloropyridazin-3-yl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate (325 mg, 1 mmol), 5-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (280 mg, 1.100 mmol), sodium carbonate (318 mg, 3.00 mmol) and PdCl2(dppf).CH2Cl2 (61.2 mg, 0.075 mmol) in dioxane (5 mL) and water (5.00 mL) was degassed by bubbling N2 for 10 minutes. After heating at 90° C. overnight, the reaction mixture was filtered through celite and washed with EtOAc. The filtrate was concentrated and the residue was purified by silica gel chromatography (0-10% MeOH/DCM) to afford (3aR,6aS)-tert-butyl 5-(6-(4-chloro-2-hydroxyphenyl)pyridazin-3-yl)hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate (180 mg, 0.432 mmol, 43.2% yield) MS (M+1)=417.0.

Workup

  1. customby bubbling N2 for 10 minutes
  2. filtrationthe reaction mixture was filtered through celite
  3. washwashed with EtOAc
  4. concentrationThe filtrate was concentrated
  5. customthe residue was purified by silica gel chromatography (0-10% MeOH/DCM)

Sources & evidence

ORD record
ord-03cd43980b7c4a67b0e6a073d070a908
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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