Binap, (A+-)- → HCID 66657090, compound

HRID 660107Notes

Reaction equation

HRID 660107 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([NH2:13])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:14][C:15]1[C:20](Br)=[CH:19][CH:18]=[CH:17][C:16]=1[O:22][CH3:23].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([NH:13][C:19]2[CH:18]=[CH:17][C:16]([O:22][CH3:23])=[C:15]([Cl:14])[CH:20]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 634876Binap, (A+-)-HCID 854071tert-butyl (3S)-3-aminopyrrolidine-1-carboxylateHCID 232878641-Bromo-2-chloro-3-methoxybenzeneHCID 23676156Sodium t-butoxide

Product 1

HCID 66657090HCID 66657090, compoundYield 77.9%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a 5 ml of toluene solution containing 0.20 g of 3(S)-aminopyrrolidine-1-carboxylic acid tert-butyl ester (1.1 mmol) and 0.238 g of 2-chloro-3-bromoanisole (1.1 mmol) were added 67.0 mg of BINAP (0.11 mmol), 24 mg of tris(dibenzylideneacetone)dipalladium (0.027 mmol) and 144 mg of sodium tert-butoxide (1.5 mmol). The mixture was heated under reflux under a nitrogen atmosphere at 100° C. for one hour. After cooling to room temperature, the reaction solution was filtered using Celite. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=10:1→3:1). The purified product was concentrated to dryness under reduced pressure to thereby obtain 0.28 g of light yellow amorphous solid 3(S)-(3-chloro-4-methoxyphenylamino)pyrrolidine-1-carboxylic acid tert-butyl ester.

Workup

  1. temperatureThe mixture was heated
  2. temperatureAfter cooling to room temperature
  3. filtrationthe reaction solution was filtered
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=10:1→3:1)
  6. concentrationThe purified product was concentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-2789913bdc0c49bc89efc88c84b6f090
Source dataset
uspto-grants-2011_12
Patent number
US08084442B2

Reaction notes

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