Sodium Bicarbonate → Tert-Butyl(2R)-4-(1-(diphenylmethyl)azetidin-3-yl)-2-methylpiperazine-1-carboxylate

HRID 707516Notes

Reaction equation

HRID 707516 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[CH2:25][NH:24][CH2:23][CH2:22][N:21]1[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27].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:24]3[CH2:23][CH2:22][N:21]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C@H:20]([CH3:19])[CH2:25]3)[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 10262201tert-Butyl (2R)-2-methylpiperazine-1-carboxylate

Product 1

HCID 118162472Tert-Butyl(2R)-4-(1-(diphenylmethyl)azetidin-3-yl)-2-methylpiperazine-1-carboxylateYield 90%

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(2R)-2-methylpiperazine-1-carboxylate (304 mg, 1.51 mmol) at room temperature. The resultant mixture was stirred at room temperature for 25 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 18 hours and 35 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, then dried over anhydrous magnesium sulfate and then filtrated. The resultant residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=5:1) to give the title compound (476 mg, yield: 90%).

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. customThe resultant residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=5:1)

Sources & evidence

ORD record
ord-4783592622404968b19a086d0c6658eb
Source dataset
uspto-grants-2015_11
Patent number
US09174998B2

Reaction notes

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