Sodium Bicarbonate → Tert-Butyl(3S)-4-(1-(diphenylmethyl)azetidin-3-yl)-3-methylpiperazine-1-carboxylate

HRID 707520Notes

Reaction equation

HRID 707520 reaction equation
[C:1]1([CH:7]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:8]2[CH2:11][C:10](=O)[CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:19][C@@H:20]1[NH:25][CH2:24][CH2:23][N:22]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:21]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>O.C(O)(=O)C.C1COCC1>[C:1]1([CH:7]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:8]2[CH2:11][CH:10]([N:25]3[CH2:24][CH2:23][N:22]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:21][C@@H:20]3[CH3:19])[CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 37355581-(Diphenylmethyl)azetidin-3-oneHCID 5049666Sodium triacetoxyborohydrideHCID 7023035(S)-1-Boc-3-methylpiperazine

Product 1

HCID 118162497Tert-Butyl(3S)-4-(1-(diphenylmethyl)azetidin-3-yl)-3-methylpiperazine-1-carboxylateYield 93%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixed solution of a commercially available product of 1-(diphenylmethyl)azetidin-3-one (300 mg, 1.26 mmol), THF (6.0 mL) and acetic acid (500 μL) was added a commercially available product of tert-butyl(3S)-3-methylpiperazine-1-carboxylate (304 mg, 1.51 mmol) at room temperature. The resultant mixture was stirred at room temperature for 1 hour and 40 minutes. Sodium triacetoxyborohydride (536 mg, 2.52 mmol) was added to the reaction mixture at room temperature, and the resultant mixture was stirred at room temperature for 13 hours and 45 minutes. Sodium hydrogen carbonate and water were added to the reaction mixture, and the resultant solution was extracted with ethyl acetate. An organic layer was washed with saturated brine and then dried over anhydrous magnesium sulfate and then filtrated. A filtrate was concentrated under a reduced pressure and the resultant residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=5:1) to give the title compound (493 mg, yield: 93%).

Workup

  1. extractionthe resultant solution was extracted with ethyl acetate
  2. washAn organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltrated
  5. concentrationA filtrate was concentrated under a reduced pressure
  6. customthe resultant residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=5:1)

Sources & evidence

ORD record
ord-f5d6a24233f244b68d81657bd2e3f68a
Source dataset
uspto-grants-2015_11
Patent number
US09174998B2

Reaction notes

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