Sodium Bicarbonate → Tert-butyl 1-(tetrahydrofuran-3-yl)azetidin-3-ylcarbamate

HRID 574809Notes

Reaction equation

HRID 574809 reaction equation
[NH:1]1[CH2:4][CH:3]([NH:5][C:6](=[O:12])[O:7][C:8]([CH3:11])([CH3:10])[CH3:9])[CH2:2]1.[O:13]1[CH2:17][CH2:16][C:15](=O)[CH2:14]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCl>[O:13]1[CH2:17][CH2:16][CH:15]([N:1]2[CH2:4][CH:3]([NH:5][C:6](=[O:12])[O:7][C:8]([CH3:9])([CH3:11])[CH3:10])[CH2:2]2)[CH2:14]1

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 5293923-OxotetrahydrofuranHCID 15194053-Aminoazetidine, 3-BOC protectedHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 67126577Tert-butyl 1-(tetrahydrofuran-3-yl)azetidin-3-ylcarbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Tert-butyl azetidin-3-ylcarbamate (0.550 g), dihydrofuran-3(2H)-one (0.412 g) and sodium triacetoxyborohydride (1.015 g) were stirred together in dichloromethane (5 mL). After stirring overnight, the reaction was poured into saturated aqueous NaHCO3 solution (25 mL) and extracted with dichloromethane (50 mL). The organic layer was washed with brine (25 mL), dried over magnesium sulfate, filtered, and concentrated. Silica gel chromatography (GraceResolv 12 g) eluting with a gradient of 0.5% to 7.5% methanol/dichloromethane over 30 minutes gave tert-butyl 1-(tetrahydrofuran-3-yl)azetidin-3-ylcarbamate. The resulting material was treated with HCl/dioxane for 1 hour, and then concentrated to give the title compound.

Workup

  1. extractionextracted with dichloromethane (50 mL)
  2. washThe organic layer was washed with brine (25 mL)
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. washSilica gel chromatography (GraceResolv 12 g) eluting with a gradient of 0.5% to 7.5% methanol/dichloromethane over 30 minutes

Sources & evidence

ORD record
ord-f296bcf48c9b4091a4994b4bf846e3c5
Source dataset
uspto-grants-2015_05
Patent number
US09034875B2

Reaction notes

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