Dimethylacetamide → 4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]benzonitrile

Participants

Role	Name	HCID	Charge
Reactant	Dimethylacetamide	HCID 31374	—
Reactant	2-[4-((1R,2R)-2-{[(4-bromobenzyl)oxy]methyl}cyclopropyl)piperidin-1-yl]-5-ethyl pyrimidine	HCID 71135272	—
Catalyst	Zinc cyanide (Zn(CN)2)	HCID 11186	—
Catalyst	Zinc	HCID 23994	—
Catalyst	Ferrocene-1,1'-bis-(diphenylphosphine)	HCID 635956	—
Catalyst	Bis(dibenzylideneacetone)palladium	HCID 9811564	—
Solvent	Diethyl Ether	HCID 3283	—
Product	4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]benzonitrile	HCID 71128806	—

Reaction Conditions

Temperature	100 °C

Reaction Steps

The product of example 54 (step A) (500 mg, 1.17 mmol), Pd2(dba)3 (43 mg, 0.046 mmol), dppf (51.5 mg, 0.093 mmol), Zn(CN)2 (89 mg, 0.755 mmol) and zinc dust (18 mg, 0.278 mmol) in DMA (1 mL) was evacuated and back-filled with argon (×3). The mixture was stirred at 100° C. for 4 h. The reaction was cooled to room temperature, diluted with Et2O and filtered through a pad of silica. The filtrate was concentrated under vacuum to leave a residue which was purified by silica gel column chromatography (elution with 5:1 hexane:ethyl acetate) to yield the title compound as a colorless gum. MS (ESI) m/z 377 [M+H]+.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09006228B2
Source dataset	uspto-grants-2015_04
ORD ID	ord-7766252cd4214ae488dd8d1d329c47ad
Source note	uspto-grants-2015_04