Ammonium Chloride → (6-chloropyridin-3-yl)(4-(tetrahydro-2H-pyran-2-yloxy)phenyl)methanone

HRID 626163

Reaction equation

I[C:2]1[CH:14]=[CH:13][C:5]([O:6][CH:7]2[CH2:12][CH2:11][CH2:10][CH2:9][O:8]2)=[CH:4][CH:3]=1.C([Li])CCC.[Cl:20][C:21]1[CH:32]=[CH:31][C:24]([C:25](N(OC)C)=[O:26])=[CH:23][N:22]=1.[Cl-].[NH4+]>O1CCCC1>[Cl:20][C:21]1[N:22]=[CH:23][C:24]([C:25]([C:2]2[CH:14]=[CH:13][C:5]([O:6][CH:7]3[CH2:12][CH2:11][CH2:10][CH2:9][O:8]3)=[CH:4][CH:3]=2)=[O:26])=[CH:31][CH:32]=1

Participants

Conditions

Temperature: -78 °C

Procedure

2-(4-Iodophenoxy)tetrahydro-2H-pyran (18.2 g, 59.9 mmol) was dissolved in 100 mL dry tetrahydrofuran and cooled to −78° C. under nitrogen atmosphere, and then n-butyllithium was added dropwise to the solution. After addition, the solution was stirred at −78° C. for 0.5 h, 6-chloro-N-methoxy-N-methylnicotinamide (8.0 g, 39.9 mmol) in 50 mL tetrahydrofuran was added dropwise and keep the temperature under −78° C. for 2 h. 100 mL of saturated aqueous ammonium chloride was added. The mixture was extracted with ethyl acetate. The extract was dried, concentrated, and purified by column chromatography to give the desired product as yellow solid (8.4 g, 66.3% yield).

Workup

additionAfter addition
customunder −78° C.
customfor 2 h
extractionThe mixture was extracted with ethyl acetate
customThe extract was dried
concentrationconcentrated
custompurified by column chromatography

Sources & evidence

ORD record: ord-2ba5a5da2adf409499e1ec215ccaba27
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09309211B2

Linked notes

Loading…