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

HRID 237296Notes

Reaction equation

HRID 237296 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].Cl.[CH3:16][O:17][NH:18][CH3:19].C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C([O-])(O)=O.[Na+]>CN(C=O)C.C(OCC)(=O)C.C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH:10]([C:12](=[O:14])[N:18]([O:17][CH3:16])[CH3:19])[CH2:11]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 516892Sodium BicarbonateHCID 27559811-Boc-Azetidine-3-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 21306970tert-Butyl 3-(methoxy(methyl)carbamoyl)azetidine-1-carboxylateYield 84.3%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of azetidine-1,3-dicarboxylic acid mono-tert-butyl ester (3.5 g, 17 mmol) in DMF (50 mL) was added O,N-dimethyl-hydroxylamine hydrochloride (3.4 g, 34 mmol), triethylamine (9.6 mL, 69 mmol), HATU (13.4 g, 34.6 mmol) and DCM (125 mL). After stirring for 16 h, saturated NaHCO3 solution and ethyl acetate were added. The aqueous portion was extracted three times with ethyl acetate. The combined organic fractions were dried (Na2SO4) and concentrated and the crude product was purified using RP HPLC (basic conditions) to provide the title compound (3.5 g, 83%) MS (ESI): mass calcd. for C11H20N2O4, 244.1; m/z found, 189.1 [M-t-Bu]+. 1H NMR (CDCl3): 4.14-4.03 (m, 2H), 4.05 (t, J=8.7 Hz, 2H), 3.66 (s, 3H), 3.63-3.59 (m, 1H), 3.21 (s, 1H), 1.43 (s, 9H).

Workup

  1. extractionThe aqueous portion was extracted three times with ethyl acetate
  2. dry with materialThe combined organic fractions were dried (Na2SO4)
  3. concentrationconcentrated
  4. customthe crude product was purified

Sources & evidence

ORD record
ord-40a93406452540969c6931a115fc53eb
Source dataset
uspto-grants-2014_02
Patent number
US08642583B2

Reaction notes

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