Hydrochloric Acid → (2S)-N,N-dibenzyl-3-[4-(cyclopropylmethyl)piperazin-1-yl]-2-methoxy-propan-1-amine

HRID 2364742Notes

Reaction equation

HRID 2364742 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(N(CC)CC)C.BrC[CH:44]1[CH2:46][CH2:45]1>ClCCl.O1CCOCC1>[CH2:27]([N:8]([CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH2:9][C@H:10]([O:25][CH3:26])[CH2:11][N:12]1[CH2:13][CH2:14][N:15]([CH2:18][CH:44]2[CH2:46][CH2:45]2)[CH2:16][CH2:17]1)[C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 81503BromomethylcyclopropaneHCID 68107497tert-butyl 4-[(2S)-3-(dibenzylamino)-2-methoxy-propyl]piperazine-1-carboxylate

Product 1

HCID 68107689(2S)-N,N-dibenzyl-3-[4-(cyclopropylmethyl)piperazin-1-yl]-2-methoxy-propan-1-amineYield 81.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

Tert-butyl 4-[(2S)-3-(dibenzylamino)-2-methoxy-propyl]piperazine-1-carboxylate 35b (2.10 g, 4.60 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 40 mL of acetonitrile. In an ice-water bath, the resulting solution was added with triethylamine (2.09 g, 20.70 mmol), stirred for 0.5 hours followed by the addition of bromomethyl-cyclopropane (0.88 g, 6.47 mmol). The reaction solution was stirred for 12 hours. The resulting solution was concentrated under reduced pressure, added with 20 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 (2S)—N,N-dibenzyl-3-[4-(cyclopropylmethyl)piperazin-1-yl]-2-methoxy-propan-1-amine 35c (1.52 g, yield: 81.3%) as a brown oil.

Workup

  1. concentrationThe resulting solution was concentrated under reduced pressure
  2. additionThe residue was added with 40 mL of acetonitrile
  3. stirringstirred for 0.5 hours
  4. stirringThe reaction solution was stirred for 12 hours
  5. concentrationThe resulting solution was concentrated under reduced pressure
  6. additionadded with 20 mL of saturated sodium bicarbonate solution
  7. extractionextracted with ethyl acetate (50 mL×3)
  8. washThe combined organic phase was washed with saturated sodium chloride solution (50 mL)
  9. dry with materialdried over anhydrous magnesium sulfate
  10. filtrationfiltered
  11. concentrationthe filtrate was concentrated under reduced pressure
  12. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-52648223c6e04ca8b07b094042497f64
Source dataset
uspto-grants-2014_04
Patent number
US08691822B2

Reaction notes

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