Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylate → tert-butyl 2-(3-(4-methylphenylsulfonamido)cyclobutoxy)-5',6'-dihydro-[3,4'-bipyridine]-1'(2'H)-carboxylate

HRID 1846821Notes

Reaction equation

HRID 1846821 reaction equation
Br[C:2]1[C:3]([O:8][CH:9]2[CH2:12][CH:11]([NH:13][S:14]([C:17]3[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=3)(=[O:16])=[O:15])[CH2:10]2)=[N:4][CH:5]=[CH:6][CH:7]=1.CC1(C)C(C)(C)OB([C:32]2[CH2:37][CH2:36][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:34][CH:33]=2)O1>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:23][C:20]1[CH:21]=[CH:22][C:17]([S:14]([NH:13][CH:11]2[CH2:12][CH:9]([O:8][C:3]3[C:2]([C:32]4[CH2:37][CH2:36][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:34][CH:33]=4)=[CH:7][CH:6]=[CH:5][N:4]=3)[CH2:10]2)(=[O:16])=[O:15])=[CH:18][CH:19]=1

Participants

6

Reactant 2

HCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 67478754N-(3-((3-bromopyridin-2-yl)oxy)cyclobutyl)-4-methylbenzenesulfonamide

Product 1

HCID 70167435tert-butyl 2-(3-(4-methylphenylsulfonamido)cyclobutoxy)-5',6'-dihydro-[3,4'-bipyridine]-1'(2'H)-carboxylateYield 70%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of N-(3-((3-bromopyridin-2-yl)oxy)cyclobutyl)-4-methylbenzenesulfonamide (397 mg, 1 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (335 mg, 1.1 mmol) and NaCO3 (212 mg, 2 mmol) in 1,4-dioxane (60 mL) and H2O (6 mL) was added Pd(dppf)Cl2 (36.6 mg, 0.05 mmol). The reaction mixture was stirred at 110° C. under N2 overnight. The reaction mixture was filtered through CELITE® and washed with CH2Cl2. The organic layer was concentrated and the crude product was purified by silica gel column to give tert-butyl 2-(3-(4-methylphenylsulfonamido)cyclobutoxy)-5′,6′-dihydro-[3,4′-bipyridine]-1′(2′H)-carboxylate (351 mg, 0.7 mmol, yield 70%). ESI-MS (M+1): 500 calc. for C26H33N3O5S 499.

Workup

  1. filtrationThe reaction mixture was filtered through CELITE®
  2. washwashed with CH2Cl2
  3. concentrationThe organic layer was concentrated
  4. customthe crude product was purified by silica gel column

Sources & evidence

ORD record
ord-487490a5d5d54791bbcbecb43109fed0
Source dataset
uspto-grants-2015_02
Patent number
US08952037B2

Reaction notes

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