Methanamine, N-methoxy-, hydrochloride (1:1) → Tert-butyl 3-[methoxy(methyl)carbamoyl]pyrrolidine-1-carboxylate

HRID 1530626Notes

Reaction equation

HRID 1530626 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([C:13]([OH:15])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:17][O:18][NH:19][CH3:20].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH3:17][O:18][N:19]([CH3:20])[C:13]([CH:10]1[CH2:11][CH2:12][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:9]1)=[O:15]

Participants

6

Reactant 4

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 27605291-((Tert-butoxy)carbonyl)pyrrolidine-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 57419605Tert-butyl 3-[methoxy(methyl)carbamoyl]pyrrolidine-1-carboxylateYield 106%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
15 °C

Procedure

A mixture of 1-(tert-butoxycarbonyl)pyrrolidine-3-carboxylic acid (5.0 g, 23 mmol), O,N-dimethylhydroxylamine hydrochloride (4.51 g, 46.5 mmol), DIPEA (9.00 g, 69.6 mmol), and HATU (17.6 g, 46.5 mmol) in DMF (50 mL) was stirred at 15° C. for 16 h. DMF was removed, the residue was extracted with ethyl acetate, washed with brine, dried over MgSO4, filtered, and evaporated to give the crude product, which was purified by silica gel chromatography eluting with a 0-30% gradient of EtOAc in petroleum ether to afford tert-butyl 3-(N-methoxy-N-methylcarbamoyl)pyrrolidine-1-carboxylate (6.3 g, 90% yield) as pale yellow oil. LCMS (ESI) m/z: 203.2 [M-56+H+].

Workup

  1. customDMF was removed
  2. extractionthe residue was extracted with ethyl acetate
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customto give the crude product, which
  8. customwas purified by silica gel chromatography
  9. washeluting with a 0-30% gradient of EtOAc in petroleum ether

Sources & evidence

ORD record
ord-7fba2dc770e94740ac687223fb0c1ff3
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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