tert-butyl (3S)-3-aminopyrrolidine-1-carboxylate → HCID 66755229, compound

HRID 1631981Notes

Reaction equation

HRID 1631981 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH3:8])[CH:3]=1.[C:9]([N:16]1[CH2:20][CH2:19][C@H:18]([NH2:21])[CH2:17]1)([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10].CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1.C(OCC)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:12]([O:11][C:9]([N:16]1[CH2:20][CH2:19][C@H:18]([NH:21][C:2]2[CH:7]=[CH:6][N:5]=[C:4]([CH3:8])[CH:3]=2)[CH2:17]1)=[O:10])([CH3:15])([CH3:13])[CH3:14]

Participants

7

Reactant 3

HCID 854071tert-butyl (3S)-3-aminopyrrolidine-1-carboxylateHCID 27628354-Bromo-2-methylpyridineHCID 23676156Sodium t-butoxide

Product 1

HCID 66755229HCID 66755229, compoundYield 96%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Procedure

4-Bromo-2-methylpyridine (165 mg, 0.96 mmol), (S)-(−)-N-Boc-3-aminopyrrolidine (214 mg, 1.15 mmol), Pd(OAc)2 (8.6 mg, 0.04 mmol), (rac)-BINAP (23.9 mg, 0.04 mmol) and NaOtBu (129 mg, 1.34 mmol) in dry toluene (5 mL) were heated at 70° C. in a flask under nitrogen atmosphere for 4 hours. The reaction mixture was allowed to cool down to room temperature, taken up in diethyl ether (10 mL), washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel using 15% MeOH in CH2Cl2 as eluent to afford (S)-3-(2-methyl-pyridin-4-ylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester (255 mg, 96%) as an orange oil.

Workup

  1. washwashed with brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash chromatography on silica gel using 15% MeOH in CH2Cl2 as eluent

Sources & evidence

ORD record
ord-cf9dd4afcc394d84b9e7343a3264f329
Source dataset
uspto-grants-2014_07
Patent number
US08791148B2

Reaction notes

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