Sodium hydride → HCID 118133431, compound

HRID 1050574Notes

Reaction equation

HRID 1050574 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[C@@H:3]1[CH3:18].[H-].[Na+]>C1COCC1.CCOC(C)=O.O>[CH3:18][C@@H:3]1[C@H:2]([N:1]2[CH2:2][CH2:3][NH:4][C:8]2=[O:9])[CH2:7][CH2:6][CH2:5][N:4]1[C:8]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:9]

Participants

6

Reactant 2

HCID 24758Sodium hydride2×HCID 53302174Benzyl (2R,3R)-3-amino-2-methylpiperidine-1-carboxylate

Product 1

HCID 118133431HCID 118133431, compoundYield 125.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

(2R,3R)-Benzyl 3-amino-2-methylpiperidine-1-carboxylate (323, 610 mg, 2.46 mmol) was dissolved in 10 mL dry THF. To it was added 2-chloroethyl isocyante (210 μL, 2.46 mmol), and the mixture was stirred at RT for 2 hours. To it was added NaH (60% in mineral oil, 120 mg, 2.95 mmol) and the mixture was stirred for overnight. Another batch of NaH (120 mg, 2.95 mmol) was then added to drive the cyclization to completion in overnight. The mixture was diluted with 150 mL EtOAc and 50 mL water. The organic phase was separated, washed with water, dried, concentrated in vacuo, and subjected to silica flash column using 0 to 4% MeOH in DCM to isolate (2R,3R)-benzyl 2-methyl-3-(2-oxoimidazolidin-1-yl)piperidine-1-carboxylate (354, 490 mg, 63%) as a white solid.

Workup

  1. additionTo it was added 2-chloroethyl isocyante (210 μL, 2.46 mmol)
  2. stirringthe mixture was stirred for overnight
  3. customin overnight
  4. customThe organic phase was separated
  5. washwashed with water
  6. customdried
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1ab1caa3bc21459783cba3843aeec1b4
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

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