Sodium hydride → Benzyl 4-((1R,2S)-2-{2-[(3-methyl-5-nitropyridin-2-yl)oxy]ethyl}cyclopropyl)piperidine-1-carboxylate

HRID 1850749Notes

Reaction equation

HRID 1850749 reaction equation
[OH:1][CH2:2][CH2:3][C@@H:4]1[CH2:6][C@@H:5]1[CH:7]1[CH2:12][CH2:11][N:10]([C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:14])[CH2:9][CH2:8]1.[H-].[Na+].Cl[C:26]1[C:31]([CH3:32])=[CH:30][C:29]([N+:33]([O-:35])=[O:34])=[CH:28][N:27]=1>CN(C=O)C>[CH3:32][C:31]1[C:26]([O:1][CH2:2][CH2:3][C@@H:4]2[CH2:6][C@@H:5]2[CH:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][CH2:16][C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)=[O:14])[CH2:9][CH2:8]2)=[N:27][CH:28]=[C:29]([N+:33]([O-:35])=[O:34])[CH:30]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 896482-Chloro-3-methyl-5-nitropyridineHCID 70856295Benzyl 4-((1R,2S)-2-(2-hydroxyethyl)cyclopropyl)piperidine-1-carboxylate

Product 1

HCID 70819067Benzyl 4-((1R,2S)-2-{2-[(3-methyl-5-nitropyridin-2-yl)oxy]ethyl}cyclopropyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To the solution of benzyl 4-[(1R,2S)-2-(2-hydroxyethyl)cyclopropyl)piperidine-1-carboxylate (3.0 g, 9.89 mmol) in 10 ml of anhydrous DMF was added NaH (0.40 g, 9.89 mmol) in small portions at RT and the final resulting solution was stirred for 15 min. Commercially available 2-chloro-3-methyl-5-nitropyridine (1.37 g, 7.91 mmol) was added in 10 portions over 2 minutes and the resulting mixture was stirred 3 hrs at RT. The reaction mixture was quenched with ice cooled aqueous sat'd NH4Cl solution and extracted with ethyl acetate/ether (1:1) (2×50 mL). The organics were combined, dried over sodium sulfate, filtered, and the filtrate concentrated under reduced pressure. The residue was purified on Biotage column (40M+ silica gel) using a gradient eluant of 0-60% ethyl acetate in hexane (800 ml) to afford the title compound. LC/MS (m/z): 440 (M+H)+.

Workup

  1. customthe final resulting solution
  2. stirringthe resulting mixture was stirred 3 hrs at RT
  3. customThe reaction mixture was quenched with ice cooled aqueous sat'd NH4Cl solution
  4. extractionextracted with ethyl acetate/ether (1:1) (2×50 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated under reduced pressure
  8. customThe residue was purified on Biotage column (40M+ silica gel)

Sources & evidence

ORD record
ord-431acc22d41b4c1680000f193ff3ea51
Source dataset
uspto-grants-2015_02
Patent number
US08957062B2

Reaction notes

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