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5-Bromonicotinamide → 5-{1'-tert-Butoxycarbonyl-4-oxospiro[chroman-2,4'-piperidin]-6-yl}nicotinamide

HRID 38474
Notes
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Reaction equation

HRID 38474 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].Br[C:34]1[CH:35]=[N:36][CH:37]=[C:38]([CH:42]=1)[C:39]([NH2:41])=[O:40].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:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C:11]2([CH2:22][C:21](=[O:23])[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([C:34]4[CH:35]=[N:36][CH:37]=[C:38]([CH:42]=4)[C:39]([NH2:41])=[O:40])[CH:19]=3)[O:14]2)[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 3

HCID 18085-BromonicotinamideHCID 10340Sodium CarbonateHCID 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 579310025-{1'-tert-Butoxycarbonyl-4-oxospiro[chroman-2,4'-piperidin]-6-yl}nicotinamide

Reagents, catalysts & solvents 4

HCID 178418397
HCID 178418397, compound
Catalyst
HCID 962WaterSolvent
HCID 6212ChloroformSolvent
HCID 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 (1.43 g, 3.23 mmol), 5-bromonicotinamide (778 mg, 3.87 mmol), Pd(PPh3)4 (372 mg, 0.322 mmol), and aqueous 2M Na2CO3 (10 ml) solution were suspended in dioxane (20 ml) and heated at 100° C. for 4 h. The reaction mixture was diluted with CHCl3 and H2O, the aqueous layer was extracted with CHCl3. The combined organic layer was dried over MgSO4. The desiccant was removed through celite filtration and the filtrate was concentrated under reduced pressure. The resulting residue was purified through silica gel column chromatography (EtOAc/Acetone) to obtain the intended compound as a pale yellow foam.

Workup

  1. extractionthe aqueous layer was extracted with CHCl3
  2. dry with materialThe combined organic layer was dried over MgSO4
  3. customThe desiccant was removed through celite filtration
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe resulting residue was purified through silica gel column chromatography (EtOAc/Acetone)

Sources & evidence

ORD record
ord-7e06f045e1ef42b1b489e3e145c87c11
Source dataset
uspto-grants-2013_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08524730B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes