Sodium Carbonate → HCID 118483468, compound

HRID 58418Notes

Reaction equation

HRID 58418 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH:10]=2)O1.Br[C:24]1[CH:29]=[CH:28][C:27]([F:30])=[C:26]([F:31])[C:25]=1[C:32]([F:35])([F:34])[F:33].C([O-])([O-])=O.[Na+].[Na+]>COCCOC.[Li+].[Cl-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:31][C:26]1[C:25]([C:32]([F:35])([F:33])[F:34])=[C:24]([C:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])[CH2:11][CH:10]=2)[CH:29]=[CH:28][C:27]=1[F:30]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 50998631HCID 50998631, compound

Product 1

HCID 118483468HCID 118483468, compoundYield 92%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 433294Lithium ChlorideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (6, 57.4 g, 185 mmol), 3 1-bromo-3,4-difluoro-2-(trifluoromethyl)benzene (48.5 g, 185 mmol), Pd(PPh3)4 (21.5 g, 18.5 mmol), and 2 M Na2CO3 (150 mL) in DME (500 mL) was heated to 80° C. for 16 h. The mixture cooled to ambient temperature and was diluted with 5% aqueous LiCl solution (100 mL). The mixture was extracted with EtOAc (3×200 mL), and the combined organic extracts were washed with brine (2×200 mL) and concentrated under reduced pressure. The residue was diluted in CH2Cl2 (100 mL) and sent through a 300 mL silica gel plug, eluting with 10% EtOAc in hexanes (800 mL). The resulting filtrate was concentrated under reduced pressure and was chromatographed over silica gel (Isco CombiFlash Rf unit, 3×330 g Redisep columns, 0% to 50% EtOAc in hexanes) to provide tert-butyl 4-(3,4-difluoro-2-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate (7) as a white solid (59.0 g, 92%): 1H NMR (300 MHz, CDCl3) 57.34-7.28 (m, 1H), 6.93 (m, 1H), 5.55 (br, 1H), 4.01 (br, 2H), 3.60 (m, 2H), 2.30 (m, 2H), 1.50 (s, 9H); MS (ESI+) m/z 308 [M+H−C4H8]+.

Workup

  1. temperatureThe mixture cooled to ambient temperature
  2. extractionThe mixture was extracted with EtOAc (3×200 mL)
  3. washthe combined organic extracts were washed with brine (2×200 mL)
  4. concentrationconcentrated under reduced pressure
  5. additionThe residue was diluted in CH2Cl2 (100 mL)
  6. washeluting with 10% EtOAc in hexanes (800 mL)
  7. concentrationThe resulting filtrate was concentrated under reduced pressure
  8. customwas chromatographed over silica gel (Isco CombiFlash Rf unit, 3×330 g Redisep columns, 0% to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-632faaa3a49e4861bcbb0f7131f3feeb
Source dataset
uspto-grants-2016_09
Patent number
US09434727B2

Reaction notes

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