Potassium Carbonate → N-Boc-pyrrolidine

HRID 2039083Notes

Reaction equation

HRID 2039083 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1C1NC(C2C=CC(C3C4C(=C(B5OC(C)(C)C(C)(C)O5)C=CC=4)C=CC=3)=CC=2)=CN=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(OC(N1CCCC1C1NC(Br)=CN=1)=O)(C)(C)C.C([O-])([O-])=O.[K+].[K+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 56605248tert-Butyl 2-(5-bromo-1H-imidazol-2-yl)pyrrolidine-1-carboxylateHCID 666210752-(5-{4-[5-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-naphthalen-1-yl]-phenyl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 643455N-Boc-pyrrolidineYield 87.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

2-(5-{4-[5-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-naphthalen-1-yl]-phenyl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (159 mg, 0.281 mmol), 2-(5-Bromo-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (178 mg (0.562 mmol), Pd(PPh3)4 (65 mg, 0.0562 mmol) and K2CO3 (0.281 mL of a 2 M aqueous solution, 0.562 mmol) were combined in 1,2-dimethoxyethane (3 mL) and degassed with bubbling N2 for 12 min. The mixture was then heated to 85° C. for 22 hours then cooled to RT, diluted with ethyl acetate (50 mL) and washed with water and brine. The organic phase was dried over magnesium sulfate and concentrated. The crude residue was purified by silica column chromatography (80% to 100% EtOAc/hexanes) to afford 2-(5-{4-[5-(1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester)-naphthalen-1-yl]-phenyl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (42 mg, 22%).

Workup

  1. customdegassed with bubbling N2 for 12 min
  2. temperaturethen cooled to RT
  3. additiondiluted with ethyl acetate (50 mL)
  4. washwashed with water and brine
  5. dry with materialThe organic phase was dried over magnesium sulfate
  6. concentrationconcentrated
  7. customThe crude residue was purified by silica column chromatography (80% to 100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-9d5474860ed7447685f5ead9488f85b4
Source dataset
uspto-grants-2013_11
Patent number
US08575118B2

Reaction notes

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