Methyl iodide → HCID 118133434, compound

HRID 1050587Notes

Reaction equation

HRID 1050587 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+].IC>C1COCC1.CCOC(C)=O.O>[CH3:18][C@@H:3]1[C@H:2]([N:1]2[CH2:7][CH2:2][CH2:3][N:4]([CH3:5])[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

7

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydride2×HCID 53302174Benzyl (2R,3R)-3-amino-2-methylpiperidine-1-carboxylate

Product 1

HCID 118133434HCID 118133434, compoundYield 185.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

(2R,3R)-Benzyl 3-amino-2-methylpiperidine-1-carboxylate (323, 270 mg, 1.09 mmol) was dissolved in 10 mL dry THF. To it was added 3-chloropropyl isocyante (112 μL, 1.09 mmol), and the mixture was stirred at RT for 3 hours. To it was added NaH (60% in mineral oil, 87 mg, 2.18 mmol) and the mixture was stirred for overnight. Another batch of NaH (87 mg, 2.18 mmol) was then added to drive the cyclization to completion in 4 hours. To the mixture was added iodomethane (540 μL, 8.64 mmol), and it was stirred at RT for overnight. It was diluted with 120 mL EtOAc and 30 mL water. The organic phase was separated, washed with water, dried, concentrated and subjected to silica flash column with 0 to 4% MeOH in DCM to isolate (2R,3R)-benzyl 2-methyl-3-(3-methyl-2-oxotetrahydropyrimidin-1(2H)-yl)piperidine-1-carboxylate (403) (350 mg, 93%) as a thick oil. It was dissolved in 100 mL MeOH, and with 10% Pd/C (0.5 g) it was hydrogenated at 40 psi on a Parr shaker for overnight. The mixture was filtered through celite, and the filtrate was concentrated in vacuo to afford 1-methyl-3-((2R,3R)-2-methylpiperidin-3-yl)tetrahydropyrimidin-2(1H)-one (404).

Workup

  1. additionTo it was added 3-chloropropyl isocyante (112 μL, 1.09 mmol)
  2. stirringthe mixture was stirred for overnight
  3. customin 4 hours
  4. stirringwas stirred at RT for overnight
  5. customThe organic phase was separated
  6. washwashed with water
  7. customdried
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-29be4c955c9f4218b9881e4acb27bdf7
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

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