Sodium Carbonate → HCID 118483541, compound

HRID 58434Notes

Reaction equation

Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([F:9])[C:3]=1[C:10]([F:13])([F:12])[F:11].CC1(C)C(C)(C)OB([C:22]2[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH:23]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.O>[F:9][C:4]1[C:3]([C:10]([F:13])([F:12])[F:11])=[C:2]([C:22]2[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH:23]=2)[CH:7]=[C:6]([F:8])[CH:5]=1

Participants

Conditions

Temperature: 85 °C

Procedure

A mixture of l-bromo-3,5-difluoro-2-(trifluoromethyl)benzene (25, 0.200 g, 0.76 mmol) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (0.237 g, 0.76 mmol), Pd(dppf) (0.056 g, 0.077 mmol), and 2 N Na2CO3 (2 mL, 4 mmol) in DME (3 mL) was heated to 85° C. for 5 h. The mixture was diluted with H2O (50 mL) and extracted with CH2Cl2 (3×75 mL). The combined organics were dried over Na2SO4, concentrated under reduced pressure, and the resulting residue was chromatographed over silica gel (24 g Redisep column, 0-25% EtOAc in hexanes) to afford tert-butyl 4-(3,5-difluoro-2-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate (26) as a light yellow oil (0.325 g, 90%). 1H NMR (300 MHz, CDCl3) δ 6.92-6.80 (m, 1H), 6.78-6.68 (m, 1H), 5.58 (s, 1H), 4.06-3.94 (m, 2H), 3.69-3.53 (m, 2H), 2.36-1.24 (m, 2H), 1.50 (s, 9H).

Workup

extractionextracted with CH2Cl2 (3×75 mL)
dry with materialThe combined organics were dried over Na2SO4
concentrationconcentrated under reduced pressure
customthe resulting residue was chromatographed over silica gel (24 g Redisep column, 0-25% EtOAc in hexanes)

Sources & evidence

ORD record: ord-1354202610c6465892b4046c4d2d61fb
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09434727B2

Reaction notes

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