Sodium Bicarbonate → Tert-Butyl(2S)-4-(1-((benzyloxy)carbonyl)azetidin-3-yl)-2-methylpiperazine-1-carboxylate

HRID 707512Notes

Reaction equation

HRID 707512 reaction equation
O=[C:2]1[CH2:5][N:4]([C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:7])[CH2:3]1.[CH3:16][C@H:17]1[CH2:22][NH:21][CH2:20][CH2:19][N:18]1[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>O.C(O)(=O)C.C1COCC1>[CH2:9]([O:8][C:6]([N:4]1[CH2:5][CH:2]([N:21]2[CH2:20][CH2:19][N:18]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C@@H:17]([CH3:16])[CH2:22]2)[CH2:3]1)=[O:7])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 10081508tert-Butyl (2S)-2-methylpiperazine-1-carboxylateHCID 10632047Benzyl 3-oxoazetidine-1-carboxylate

Product 1

HCID 118162427Tert-Butyl(2S)-4-(1-((benzyloxy)carbonyl)azetidin-3-yl)-2-methylpiperazine-1-carboxylateYield 64.5%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixed solution of benzyl 3-oxoazetidine-1-carboxylate (30.0 g, 146 mmol), which is a known and commercially available product, THF (100 mL) and acetic acid (60 mL) was added a commercially available product of tert-butyl(2S)-2-methylpiperazine-1-carboxylate (32.2 g, 161 mmol) at room temperature. The resultant mixture was stirred at room temperature for 1 hour. To the reaction mixture was added sodium triacetoxyborohydride (46.5 g, 219 mmol) at 0° C. The resultant mixture was stirred at room temperature for 1 hour and 30 minutes. To the reaction mixture were added sodium hydrogen carbonate and water at 0° C. The resultant solution was extracted with ethyl acetate. An organic layer was dried over anhydrous magnesium sulfate and then filtrated. The solvent was evaporated 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 (36.7 g, yield: 64%).

Workup

  1. extractionThe resultant solution was extracted with ethyl acetate
  2. dry with materialAn organic layer was dried over anhydrous magnesium sulfate
  3. filtrationfiltrated
  4. customThe solvent was evaporated under a reduced pressure
  5. customthe resultant residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=5:1)

Sources & evidence

ORD record
ord-7fc803a242394cb49d0779fd1dc78a24
Source dataset
uspto-grants-2015_11
Patent number
US09174998B2

Reaction notes

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