4-Methylmorpholine → Tert-butyl 2-[[(4-bromobenzoyl)amino]methyl]pyrrolidine-1-carboxylate

HRID 1185648

Reaction equation

HRID 1185648 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[CH2:13][NH2:14])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br:15][C:16]1[CH:24]=[CH:23][C:19]([C:20](O)=[O:21])=[CH:18][CH:17]=1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[CH2:13][NH:14][C:20](=[O:21])[C:19]1[CH:23]=[CH:24][C:16]([Br:15])=[CH:17][CH:18]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 114644-Bromobenzoic acidHCID 2756484(+-)-2-(Aminomethyl)-1-N-Boc-pyrrolidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 58185404Tert-butyl 2-[[(4-bromobenzoyl)amino]methyl]pyrrolidine-1-carboxylateYield 100%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 2-aminomethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (1.00 g, 4.97 mmol) and 4-bromo-benzoic acid (996 mg, 4.97 mmol) in DMF (25 mL) was added N-methylmorpholine (655 μl, 5.96 mmol) and HATU (1.89 g, 4.97 mmol). After stirring for 3 hours the reaction was concentrated then diluted with EtOAc and washed with 1N HCl, saturated NaHCO3, and brine. The organic phase was then dried over Na2SO4 and concentrated. The crude material was purified by silica gel chromatography (20-50% EtOAc-hexanes gradient) to afford 2-[(4-bromo-benzoylamino)-methyl]-pyrrolidine-1-carboxylic acid tert-butyl ester (1.91 g, 4.97 mmol, quantitative yield). LCMS-ESI+: calc'd for C17H24BrN2O3: 383.1 (M+H+). Found: 383.6

Workup

  1. concentrationwas concentrated
  2. additionthen diluted with EtOAc
  3. washwashed with 1N HCl, saturated NaHCO3, and brine
  4. dry with materialThe organic phase was then dried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude material was purified by silica gel chromatography (20-50% EtOAc-hexanes gradient)

Sources & evidence

ORD record
ord-4f08e861e34d4ba7bf744d2c9a8050e3
Source dataset
uspto-grants-2014_03
Patent number
US08669234B2

Linked notes

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