1,2-Dimethoxyethane → tert-butyl 5-(2-fluoropyridin-3-yl)-3,4-dihydropyridine-1(2H)-carboxylate

HRID 410279Notes

Reaction equation

[F:1][C:2]1[C:7](I)=[CH:6][CH:5]=[CH:4][N:3]=1.CC1(C)C(C)(C)OB([C:17]2[CH2:18][CH2:19][CH2:20][N:21]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH:22]=2)O1.O.C(=O)([O-])[O-].[Na+].[Na+].COCCOC>O.C(OCC)(=O)C.C(O)C>[F:1][C:2]1[C:7]([C:19]2[CH2:18][CH2:17][CH2:22][N:21]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH:20]=2)=[CH:6][CH:5]=[CH:4][N:3]=1

Participants

Conditions

Temperature: 140 °C

Procedure

A microwave vial was charged with 2-fluoro-3-iodopyridine (1.325 g, 5.94 mmol), tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydropyridine-1(2H)-carboxylate (1.8 g, 5.82 mmol), sodium carbonate hydrate (2166 mg, 17.46 mmol), catalyst (211 mg, 0.301 mmol), DME (3 mL), Ethanol (0.857 mL) and Water (1.286 mL). The vial was capped and heated in a Biotage Initiator to 140° C. for 15 minutes. The reaction was diluted with water (20 ml) and ethyl acetate (30 ml). The organic layer was washed with water (2×10 mL), brine (10 mL), and concentrated in vacuo. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep® pre-packed silica gel column (40 g), eluting with 0% to 50% EtOAc in hexane, to provide tert-butyl 5-(2-fluoropyridin-3-yl)-3,4-dihydropyridine-1(2H)-carboxylate (673 mg, 2.418 mmol) as a colorless syrup. [M+Na]=332.1.

Workup

customThe vial was capped
washThe organic layer was washed with water (2×10 mL), brine (10 mL)
concentrationconcentrated in vacuo
customchromatographed through a Redi-Sep® pre-packed silica gel column (40 g)
washeluting with 0% to 50% EtOAc in hexane

Sources & evidence

ORD record: ord-7998028be97247789de3a47727ff0e8d
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08759532B2

Reaction notes

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