Ethyl Acetate → 3-amino-6-trifluoromethyl-3',6'-dihydro-2'H-[2,4']bipyridinyl-1'-carboxylic acid tert-butyl ester

HRID 1896628Notes

Reaction equation

[NH2:1][C:2]1[C:3](Cl)=[N:4][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:7]=1.[C:13]([O:17][C:18]([N:20]1[CH2:25][CH:24]=[C:23](B2OC(C)(C)C(C)(C)O2)[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(OCC)(=O)C>COCCOC>[C:13]([O:17][C:18]([N:20]1[CH2:21][CH:22]=[C:23]([C:3]2[C:2]([NH2:1])=[CH:7][CH:6]=[C:5]([C:8]([F:11])([F:10])[F:9])[N:4]=2)[CH2:24][CH2:25]1)=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of 3-amino-2-chloro-6-trifluoromethyl-pyridine (0.890 g), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (1.4 g) (prepared as described in WO 2006/003494) and tetrakis(triphenyl-phosphine)palladium (0.200 g) in 1,2-dimethoxyethane (45 ml) was treated with aqueous potassium phosphate (1.1 M) (1.92 g). The reaction mixture was stirred at 80° C. for 3 hours. Aqueous workup with ethyl acetate furnished a residue which was purified by chromatography on silica gel (eluent: hexane/ethyl acetate 1:1) to give 3-amino-6-trifluoromethyl-3′,6′-dihydro-2′H-[2,4]bipyridinyl-1′-carboxylic acid tert-butyl ester (1.5 g) as a white solid. MS (ES+) 288 (M-isoprene); 1H NMR (400 MHz, CDCl3) 1.50 (s, 9H), 2.61 (m, 2H), 3.67 (t, 2H), 4.10 (m, 2H), 4.21 (s, 2H), 6.11 (s, 1H), 7.03 (d, 1H), 7.33 (d, 1H).

Workup

customwas purified by chromatography on silica gel (eluent: hexane/ethyl acetate 1:1)

Sources & evidence

ORD record: ord-4f620acd46fd47249cb7a043a606ea5a
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08518971B2

Reaction notes

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