Ammonia → (2S)-N,N-dibenzyl-2-methoxy-3-(4-methylpiperazin-1-yl)propan-1-amine

HRID 2364747Notes

Reaction equation

HRID 2364747 reaction equation
[CH2:1]([N:8]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:9][C@H:10]([O:25][CH3:26])[CH2:11][N:12]1[CH2:17][CH2:16][N:15]([C:18](OC(C)(C)C)=O)[CH2:14][CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.C=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].N>ClCCl.O1CCOCC1.O.C(#N)C>[CH2:27]([N:8]([CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[CH2:9][C@H:10]([O:25][CH3:26])[CH2:11][N:12]1[CH2:13][CH2:14][N:15]([CH3:18])[CH2:16][CH2:17]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

10

Reactant 5

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 68107497tert-butyl 4-[(2S)-3-(dibenzylamino)-2-methoxy-propyl]piperazine-1-carboxylate

Product 1

HCID 68107005(2S)-N,N-dibenzyl-2-methoxy-3-(4-methylpiperazin-1-yl)propan-1-amineYield 83%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

Tert-butyl 4-[(2S)-3-(dibenzylamino)-2-methoxy-propyl]piperazine-1-carboxylate 35b (4.36 g, 9.60 mmol) was dissolved in 30 mL of dichloromethane followed by the addition of 20 mL of a 4 M solution of hydrogen chloride in dioxane. The reaction solution was stirred for 0.5 hours. The resulting solution was concentrated under reduced pressure. The residue was added with 30 mL of acetonitrile, 30 mL of water and formaldehyde (0.58 g, 19.20 mmol) successively. The reaction solution was stirred for 0.5 hours, added with sodium triacetoxyborohydride (6.10 g, 28.80 mmol). The reaction solution was stirred for 1 hour. The resulting solution was added dropwise with aqueous ammonia to adjust pH to 9 to 10 and extracted with ethyl acetate (50 mL×3). The combined organic phase was washed with saturated sodium chloride solution (20 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 (2S)—N,N-dibenzyl-2-methoxy-3-(4-methylpiperazin-1-yl)propan-1-amine 38a (2.90 g, yield: 83.0%) as a brown oil.

Workup

  1. concentrationThe resulting solution was concentrated under reduced pressure
  2. stirringThe reaction solution was stirred for 0.5 hours
  3. stirringThe reaction solution was stirred for 1 hour
  4. extractionextracted with ethyl acetate (50 mL×3)
  5. washThe combined organic phase was washed with saturated sodium chloride solution (20 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-7bdfb95894a24fa5a4edd9947a81bb69
Source dataset
uspto-grants-2014_04
Patent number
US08691822B2

Reaction notes

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