Oxygen → 1-(Tert-butoxycarbonyl)-2-methyl-4-(4,5-difluorobenzofur-7-yl)-1,2,3,6-tetrahydropyridine

HRID 1815878Notes

Reaction equation

HRID 1815878 reaction equation
[F:1][C:2]1[C:7]2[CH:8]=[CH:9][O:10][C:6]=2[C:5](B(O)O)=[CH:4][C:3]=1[F:14].[C:15]([O:19][C:20]([N:22]1[CH2:27][CH:26]=[C:25](OS(C(F)(F)F)(=O)=O)[CH2:24][CH:23]1[CH3:36])=[O:21])([CH3:18])([CH3:17])[CH3:16].P([O-])([O-])([O-])=O.[K+].[K+].[K+].O=O>O1CCCC1.C1(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)C=CC=CC=1.C(OCC)C>[C:15]([O:19][C:20]([N:22]1[CH2:27][CH:26]=[C:25]([C:5]2[C:6]3[O:10][CH:9]=[CH:8][C:7]=3[C:2]([F:1])=[C:3]([F:14])[CH:4]=2)[CH2:24][CH:23]1[CH3:36])=[O:21])([CH3:18])([CH3:16])[CH3:17]

Participants

8

Reactant 4

HCID 977OxygenHCID 62657Potassium Phosphate, TribasicHCID 224955901,1-Dimethylethyl 2-methyl-4-{[(trifluoromethyl)sulfonyl]oxy}-3,6-dihydro-1(2H)-pyridinecarboxylateHCID 22495642(4,5-Difluorobenzofuran-7-yl)boronic acid

Product 1

HCID 224956761-(Tert-butoxycarbonyl)-2-methyl-4-(4,5-difluorobenzofur-7-yl)-1,2,3,6-tetrahydropyridineYield 74%

Reagents, catalysts & solvents 3

HCID 178420554HCID 178420554, compoundCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 0.5 gm (2.53 mMol) 4,5-difluorobenzofur-7-ylboronic acid, 0.872 gm (2.53 mMol) 1-(tert-butoxycarbonyl)-2-methyl-4-trifluoromethanesulfonyloxy-1,2,3,6-tetrahydropyridine, 0.806 gm (3.8 mMol) potassium phosphate, and 0.146 gm (0.127 mMol) tetrakis(triphenylphosphino)palladium in 10 mL tetrahydrofuran was placed under vacuum and pressurized with nitrogen three times to exclude oxygen. The reaction mixture was heated at reflux for 3 hours and was then poured into 250 mL diethyl ether and filtered through a pad of celite. The filter pad was washed with 200 mL diethyl ether and the combined filtrates were concentrated under reduced pressure. The residue was subjected to silica gel chromatography, eluting with hexane followed by 9% ethyl acetate in hexane. Fractions containing the desired product were combined and concentrated under reduced pressure to provide 0.65 gm (74%) 1-(tert-butoxycarbonyl)-2-methyl-4-(4,5-difluorobenzofur-7-yl)-1,2,3,6-tetrahydropyridine. A solution of 0.62 gm (1.77 mMol) 1-(tert-butoxycarbonyl)-2-methyl-4-(4,5-difluorobenzofur-7-yl)-1,2,3,6-tetrahydropyridine in 10 mL 4 M hydrogen chloride in dioxane was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure and the residue slurried in diethyl ether to provide 0.44 gm (86%) of the title compound.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 3 hours
  3. filtrationfiltered through a pad of celite
  4. washThe filter pad was washed with 200 mL diethyl ether
  5. concentrationthe combined filtrates were concentrated under reduced pressure
  6. washeluting with hexane
  7. additionFractions containing the desired product
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ea896e1ce8bd4e2d94864a5a200b472a
Source dataset
uspto-grants-2005_04
Patent number
US06881733B1

Reaction notes

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