Acetic Acid → tert-Butyl 3-(3-(acrylamido)azetidin-1-yl)azetidine-1-carboxylate

HRID 588797Notes

Reaction equation

HRID 588797 reaction equation
Cl.[NH:2]1[CH2:5][CH:4]([NH:6][C:7](=[O:10])[CH:8]=[CH2:9])[CH2:3]1.O=[C:12]1[CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13]1.CCN(CC)CC.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl.O>[C:7]([NH:6][CH:4]1[CH2:5][N:2]([CH:12]2[CH2:13][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15]2)[CH2:3]1)(=[O:10])[CH:8]=[CH2:9]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 8471TriethylamineHCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterHCID 5049666Sodium triacetoxyborohydrideHCID 131734447N-(azetidin-3-yl)acrylamide hydrochloride

Product 1

HCID 90462701tert-Butyl 3-(3-(acrylamido)azetidin-1-yl)azetidine-1-carboxylateYield 31.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of N-(azetidin-3-yl)acrylamide hydrochloride (500 mg, 3.40 mmol), tert-butyl 3-oxoazetidine-1-carboxylate (684 mg, 4.0 mmol), Et3N (343 mg, 3.40 mmol) and AcOH (100 mg, 0.167 mmol) in DCM (20 mL), NaBH(OAc)3 (2.16 g, 10.2 mmol) was added, and the resulting mixture was stirred at room temperature for 16 h. The mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated NaHCO3 solution and brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (DCM/MeOH=100:1 to 20:1) to afford the desired product (300 mg, 31% yield).

Workup

  1. additionwas added
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with saturated NaHCO3 solution and brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column chromatography on silica gel (DCM/MeOH=100:1 to 20:1)

Sources & evidence

ORD record
ord-e9802b4dc8954c3b8a8cb1df8bb1e09b
Source dataset
uspto-grants-2016_01
Patent number
US09227978B2

Reaction notes

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