Sodium hydride → Tert-butyl 3-(3'-(methylamino)-3,4'-bipyridin-2-yloxy)azetidine-1-carboxylate

HRID 878377Notes

Reaction equation

HRID 878377 reaction equation
[OH:1][CH:2]1[CH2:5][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:3]1.[H-].[Na+].Cl[C:16]1[C:21]([C:22]2[CH:27]=[CH:26][N:25]=[CH:24][C:23]=2[N:28](C)[C:29](=O)C2C=C(C(F)(F)F)C=C(S(C)(=O)=O)C=2)=[CH:20][CH:19]=[CH:18][N:17]=1.[NH4+].[Cl-]>CN(C=O)C.CCOC(C)=O>[CH3:29][NH:28][C:23]1[CH:24]=[N:25][CH:26]=[CH:27][C:22]=1[C:21]1[C:16]([O:1][CH:2]2[CH2:3][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:5]2)=[N:17][CH:18]=[CH:19][CH:20]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 2756801Tert-butyl 3-hydroxyazetidine-1-carboxylateHCID 86670825N-(2-Chloro-[3,4']bipyridinyl-3'-yl)-3-methanesulfonyl-N-methyl-5-trifluoromethyl-benzamide

Product 1

HCID 70663657Tert-butyl 3-(3'-(methylamino)-3,4'-bipyridin-2-yloxy)azetidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of tert-butyl 3-hydroxyazetidine-1-carboxylate (81.1 mg, 468 μmol, Fluorochem) in DMF (1 mL) was added sodium hydride (approx. 55% in mineral oil) (18.6 mg, 426 μmol) and the resulting suspension was stirred at room temperature for 30 minutes until gas evolution ceased. To the turbid solution was added N-(2-chloro-3,4′-bipyridin-3′-yl)-N-methyl-3-(methylsulfonyl)-5-(trifluoromethyl)benzamide (0.1 g, 213 μmol) in one portion. The light brown reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was poured on saturated aqueous NH4Cl solution and EtOAc and the layers were separated. The aqueous layer was extracted twice with EtOAc. The organic layers were washed twice with water and once with brine, dried over MgSO4, filtered and evaporated. The product was purified by preparative HPLC (Gemini NX column) using a gradient of MeOH:water (containing 0.1% formic acid) (20:80 to 98:2). Colorless oil (0.027 g; 35%). MS (ESI): m/z=357.19 [M+H]+.

Workup

  1. stirringThe light brown reaction mixture was stirred at room temperature for 3 hours
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted twice with EtOAc
  4. washThe organic layers were washed twice with water and once with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe product was purified by preparative HPLC (Gemini NX column)

Sources & evidence

ORD record
ord-dbbbf92151934d2b8fb8cf1d647fe198
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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