1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → Carbamic acid, N-[1-(6-hydroxy-3-quinolinyl)-3-pyrrolidinyl]-, 1,1-dimethylethyl ester

HRID 2175136Notes

Reaction equation

HRID 2175136 reaction equation
C([O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]=[CH:10][C:9](Br)=[CH:8]2)(=O)C.[NH:16]1[CH2:20][CH2:19][CH:18]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:17]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CC([O-])(C)C.[K+]>CN(C=O)C.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]>[OH:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]=[CH:10][C:9]([N:16]1[CH2:20][CH2:19][CH:18]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:26])([CH3:25])[CH3:27])[CH2:17]1)=[CH:8]2

Participants

7

Reactant 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 2757234tert-butyl N-(pyrrolidin-3-yl)carbamateHCID 23665647Potassium tert-butoxideHCID 685300473-Bromoquinolin-6-yl acetate

Product 1

HCID 86696256Carbamic acid, N-[1-(6-hydroxy-3-quinolinyl)-3-pyrrolidinyl]-, 1,1-dimethylethyl esterYield 12%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of Intermediate A (1.50 g, 5.07 mmol), tert-butyl pyrrolidin-3-ylcarbamate (1.13 g, 6.09 mmol), Pd2(dba)3 (0.232 g, 0.254 mmol), Xantphos (0.294 g, 0.507 mmol) and KOtBu (1.14 g, 10.2 mmol) in DMF (15 mL) was bubbled with argon for 20 min. The result mixture was heated at 110° C. overnight. The solution was cooled to rt and the solvent was removed under reduced pressure. The residue was diluted with water, extracted with DCM three times. The combined organic phase was dried over anhydrous Na2SO4, filtered and concentrated. The crude product was purified by chromatography (eluting with 5% MeOH in DCM) to give the title compound as yellow solid (0.2 g, yield 11%). LCMS (method N): [M+H]+=330, tR=1.93 min.

Workup

  1. customwas bubbled with argon for 20 min
  2. temperatureThe solution was cooled to rt
  3. customthe solvent was removed under reduced pressure
  4. additionThe residue was diluted with water
  5. extractionextracted with DCM three times
  6. dry with materialThe combined organic phase was dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by chromatography (eluting with 5% MeOH in DCM)

Sources & evidence

ORD record
ord-dc9dd3fcf64d4589bb1e0468547c6b64
Source dataset
uspto-grants-2015_06
Patent number
US09062045B2

Reaction notes

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