Methyl iodide → tert-butyl 4-[(2S)-3-(dibenzylamino)-2-methoxy-propyl]piperazine-1-carboxylate

HRID 2364741Notes

Reaction equation

HRID 2364741 reaction equation
[H-].[Na+].[CH2:3]([N:10]([CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[CH2:11][C@H:12]([OH:27])[CH2:13][N:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.CI.[C:37](=O)(O)[O-].[Na+]>O1CCCC1>[CH2:3]([N:10]([CH2:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)[CH2:11][C@H:12]([O:27][CH3:37])[CH2:13][N:14]1[CH2:15][CH2:16][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:18][CH2:19]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 68107746tert-butyl 4-[(2S)-3-(dibenzylamino)-2-hydroxy-propyl]piperazine-1-carboxylate

Product 1

HCID 68107497tert-butyl 4-[(2S)-3-(dibenzylamino)-2-methoxy-propyl]piperazine-1-carboxylateYield 56%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride (333 mg, 8.30 mmol) was dissolved in 50 mL of tetrahydrofuran, added dropwise with a solution of tert-butyl 4-[(2S)-3-(dibenzylamino)-2-hydroxy-propyl]piperazine-1-carboxylate 35a (3.65 g, 8.30 mmol) in tetrahydrofuran in an ice-water bath. The reaction solution was stirred for 10 minutes and warmed up to room temperature. The reaction solution was stirred for 1 hour and cooled down to 0° C. followed by the addition of methyl iodide (1.18 g, 8.30 mmol). The reaction solution was stirred for 12 hours. The resulting solution was added with 10 mL of saturated sodium bicarbonate solution and extracted with ethyl acetate (50 mL×3). The combined organic phase was washed with saturated sodium chloride solution (50 mL), then dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound tert-butyl 4-[(2S)-3-(dibenzylamino)-2-methoxy-propyl]piperazine-1-carboxylate 35b (2.10 g, yield: 56.0%) as a yellow oil.

Workup

  1. stirringThe reaction solution was stirred for 1 hour
  2. temperaturecooled down to 0° C.
  3. stirringThe reaction solution was stirred for 12 hours
  4. extractionextracted with ethyl acetate (50 mL×3)
  5. washThe combined organic phase was washed with saturated sodium chloride solution (50 mL)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-973774c2d22741f3b91ea399d2d94df4
Source dataset
uspto-grants-2014_04
Patent number
US08691822B2

Reaction notes

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