Triethylamine → tert-Butyl 3-(methoxy(methyl)carbamoyl)azetidine-1-carboxylate

HRID 1485110Notes

Reaction equation

HRID 1485110 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([C:12]([OH:14])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[CH3:28][NH:29][O:30][CH3:31].C(N(CC)CC)C>O1CCCC1.C(#N)C>[CH3:31][O:30][N:29]([CH3:28])[C:12]([CH:10]1[CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:11]1)=[O:14]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 27559811-Boc-Azetidine-3-carboxylic acid

Product 1

HCID 21306970tert-Butyl 3-(methoxy(methyl)carbamoyl)azetidine-1-carboxylateYield 120.3%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-(tert-butoxycarbonyl)azetidine-3-carboxylic acid (5.00 g) in tetrahydrofuran (62.1 mL), 1,1′-carbonyldiimidazole (6.05 g) was added and the mixture was stirred at room temperature for an hour. To the reaction mixture, a solution of N,O-dimethylhydroxylamine hydrochloride (3.64 g) and triethylamine (4.02 g) in acetonitrile (62.1 mL) was added and the mixture was stirred at the same temperature for 15 hours. The reaction mixture was concentrated under reduced pressure and water was added to the resulting residue. Extraction was conducted with ethyl acetate and the combined organic layers were washed with an aqueous solution of 5% citric acid and saturated brine. The washed organic layers were dried over anhydrous sodium sulfate and after removing the desiccant by filtration, the filtrate was concentrated under reduced pressure to give tert-butyl 3-[methoxy(methyl)carbamoyl]azetidine-1-carboxylate as a pale yellow oil (7.30 g).

Workup

  1. stirringthe mixture was stirred at the same temperature for 15 hours
  2. concentrationThe reaction mixture was concentrated under reduced pressure and water
  3. additionwas added to the resulting residue
  4. extractionExtraction
  5. washthe combined organic layers were washed with an aqueous solution of 5% citric acid and saturated brine
  6. dry with materialThe washed organic layers were dried over anhydrous sodium sulfate
  7. customafter removing the
  8. filtrationdesiccant by filtration
  9. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-141f3940ec07426886c18291e1345906
Source dataset
uspto-grants-2016_08
Patent number
US09422240B2

Reaction notes

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