4-Methylmorpholine → HCID 688299, compound

HRID 2279455Notes

Reaction equation

HRID 2279455 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[C:13]([OH:15])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.C(Cl)(=O)OCC.Cl.[CH3:30][O:31][NH:32][CH3:33]>C(Cl)Cl>[CH3:30][O:31][N:32]([CH3:33])[C:13]([C@H:9]1[CH2:10][CH2:11][CH2:12][N:8]1[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[O:15]

Participants

6

Reactant 4

HCID 79724-Methylmorpholine2×HCID 10928Ethyl chloroformateHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 688022(2R)-1-[(tert-butoxy)carbonyl]pyrrolidine-2-carboxylic acid

Product 1

HCID 688299HCID 688299, compoundYield 68.03%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (R)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid (11.93 g, 55.42 mmol) and DCM (70 mL) cooled to −15° C. was added a solution of NMM (5.79 g, 57.3 mmol), ethyl carbonochloridate (12.03 g, 110.8 mmol) and DCM (50 mL) and the mixture was stirred for 15 min. Additional NMM (11.59 g, 114.5 mmol) was added followed by portion wise addition of O,N-dimethylhydroxylamine hydrochloride (10.81 g, 110.8 mmol). The reaction was stirred at RT for 18 h. The reaction was poured onto water and extracted with DCM. The organic layer was dried, filtered, and concentrated and the crude residue was purified by SiO2 chromatography eluting with EtOAc/hexane (1:1) to afford 9.74 g (68.03%) of (R)-tert-butyl 2-(methoxy(methyl)carbamoyl)pyrrolidine-1-carboxylate (74).

Workup

  1. stirringThe reaction was stirred at RT for 18 h
  2. additionThe reaction was poured onto water
  3. extractionextracted with DCM
  4. customThe organic layer was dried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customthe crude residue was purified by SiO2 chromatography
  8. washeluting with EtOAc/hexane (1:1)

Sources & evidence

ORD record
ord-00f5db4843c540a5bb5e8ebe5fdd1a15
Source dataset
uspto-grants-2015_09
Patent number
US09133187B2

Reaction notes

Loading…