Sodium Carbonate → tert-Butyl 6-(5-carbamoylpyridin-2-yl)-4-oxospiro[chroman-2,4'-piperidine]-1'-carboxylate

HRID 38478

Reaction equation

HRID 38478 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2([CH2:22][C:21](=[O:23])[C:20]3[C:15](=[CH:16][CH:17]=[C:18](B4OC(C)(C)C(C)(C)O4)[CH:19]=3)[O:14]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:34]1[CH:42]=[CH:41][C:37]([C:38]([NH2:40])=[O:39])=[CH:36][N:35]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C(Cl)(Cl)Cl.O.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>[C:38]([C:37]1[CH:41]=[CH:42][C:34]([C:18]2[CH:19]=[C:20]3[C:15](=[CH:16][CH:17]=2)[O:14][C:11]2([CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH2:10]2)[CH2:22][C:21]3=[O:23])=[N:35][CH:36]=1)(=[O:39])[NH2:40]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 804566-ChloronicotinamideHCID 579309611'-Tert-butoxycarbonyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)spiro[chroman-2,4'-piperidin]-4-one

Product 1

HCID 58208682tert-Butyl 6-(5-carbamoylpyridin-2-yl)-4-oxospiro[chroman-2,4'-piperidine]-1'-carboxylate

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6212ChloroformSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

1′-tert-butoxycarbonyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)spiro[chroman-2,4′-piperidin]-4-one (40.0 g, 90.0 mmol), 6-chloronicotinamide (17.0 g, 108 mmol), Pd(PPh3)4 (5.21 g, 4.51 mmol), and aqueous 2M Na2CO3 (100 ml) solution were suspended in dioxane (300 ml) and heated at 100° C. for 16 h. The reaction mixture was diluted with CHCl3 and H2O, the aqueous layer was extracted with CHCl3. The combined organic layer was washed with brine, dried over MgSO4 and silicagel. The desiccant was removed through celite filtration and the filtrate was concentrated under reduced pressure. The resulting residue was purified by crystallization (CHCl3-EtOAc) to obtain the intended compound as a colorless solid.

Workup

  1. extractionthe aqueous layer was extracted with CHCl3
  2. washThe combined organic layer was washed with brine
  3. dry with materialdried over MgSO4 and silicagel
  4. customThe desiccant was removed through celite filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe resulting residue was purified by crystallization (CHCl3-EtOAc)

Sources & evidence

ORD record
ord-71529f5fb4fa4deb990dc0de44b47136
Source dataset
uspto-grants-2013_09
Patent number
US08524730B2

Linked notes

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