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Sodium t-butoxide → Tert-butyl 3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxo-1,4'-bipiperidine-1'-carboxylate

HRID 407935
Notes
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Reaction equation

HRID 407935 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)[C:3]1=[O:21].Br[C:23]1[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:25][C:24]=1[F:33].CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:33][C:24]1[CH:25]=[C:26]([S:29]([CH3:32])(=[O:31])=[O:30])[CH:27]=[CH:28][C:23]=1[NH:1][CH:2]1[CH2:7][CH2:6][CH2:5][N:4]([CH:8]2[CH2:9][CH2:10][N:11]([C:14]([O:16][C:17]([CH3:18])([CH3:20])[CH3:19])=[O:15])[CH2:12][CH2:13]2)[C:3]1=[O:21]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 3

HCID 23676156Sodium t-butoxideHCID 467389084-Bromo-3-fluorophenyl methyl sulphoneHCID 66802275(S)-tert-butyl 3-amino-2-oxo-1,4'-bipiperidine-1'-carboxylate

Product 1

HCID 66802697Tert-butyl 3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxo-1,4'-bipiperidine-1'-carboxylateYield 106%

Reagents, catalysts & solvents 3

HCID 634876
Binap, (A+-)-
Catalyst
HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst
HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

(S)-tert-Butyl 3-amino-2-oxo-1,4′-bipiperidine-1′-carboxylate (Example 39, Steps A-C, 5.0 g, 17 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (1.0 g, 1.7 mmol), 1-bromo-2-fluoro-4-(methylsulfonyl)benzene (6.4 g, 25 mmol) and NaOtBu (1.9 g, 20 mmol) were dissolved in degassed toluene (100 mL). Pd2 dba3 (0.77 g, 0.84 mmol) was added and the reaction heated in an 80° C. oil bath for 5 hours. The reaction was concentrated and purified over silica gel (50-100% EtOAc in hexanes followed by 5% ammoniated methanol in CH2Cl2) to afford tert-butyl 3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxo-1,4′-bipiperidine-1′-carboxylate (8.4 g, 18 mmol, 106% yield) as yellow solid.

Workup

  1. concentrationThe reaction was concentrated
  2. custompurified over silica gel (50-100% EtOAc in hexanes followed by 5% ammoniated methanol in CH2Cl2)

Sources & evidence

ORD record
ord-4179f3243d2248b9a0443f98bb7f97a1
Source dataset
uspto-grants-2014_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08754226B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes