Binap, (A+-)- → HCID 59352705, compound

HRID 2385559Notes

Reaction equation

HRID 2385559 reaction equation
Br[C:2]1[CH:28]=[CH:27][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]3([C:19]4[CH:20]=[C:21]([F:25])[C:22]([F:24])=[CH:23][C:18]=4[O:17][CH2:16]3)[C:8]2=[O:26])=[CH:4][CH:3]=1.C1(C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C(=CC=CC=2)C=CC=1P(C1C=CC=CC=1)C1C=CC=CC=1.[C:75]([N:82]1[CH2:86][CH2:85][C@@H:84]([NH2:87])[CH2:83]1)([O:77][C:78]([CH3:81])([CH3:80])[CH3:79])=[O:76].CC(C)([O-])C.[Na+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:25][C:21]1[C:22]([F:24])=[CH:23][C:18]2[O:17][CH2:16][C:9]3([C:10]4[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=4)[N:7]([CH2:6][C:5]4[CH:4]=[CH:3][C:2]([NH:87][C@@H:84]5[CH2:85][CH2:86][N:82]([C:75]([O:77][C:78]([CH3:81])([CH3:80])[CH3:79])=[O:76])[CH2:83]5)=[CH:28][CH:27]=4)[C:8]3=[O:26])[C:19]=2[CH:20]=1

Participants

7

Reactant 4

HCID 634876Binap, (A+-)-HCID 854070(R)-(+)-1-Boc-3-aminopyrrolidineHCID 23676156Sodium t-butoxideHCID 593524831'-(4-bromobenzyl)-5,6-difluorospiro[1-benzofuran-3,3'-indol]-2'(1'H)-one

Product 1

HCID 59352705HCID 59352705, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

To a solution of 1′-(4-bromobenzyl)-5,6-difluorospiro[1-benzofuran-3,3′-indol]-2′(1′H)-one (0.44 g, 1.0 mmol) in anhydrous toluene (10 mL) was added (±)-(1,1′-binaphthalene-2,2′-diyl)bis(diphenylphosphine) (0.093 g, 0.15 mmol) and (R)-(+)-1-Boc-3-aminopyrrolidine (0.26 g, 1.4 mmol), followed by tris(dibenzylideneacetone)dipalladium (0) (0.458 g, 0.1 mmol) and sodium tert-butoxide (0.19 g, 2.0 mmol). The reaction mixture was heated at reflux for 16 h, allowed to cool to ambient temperature and filtered through a pad of diatomaceous earth. The filtrate was concentrated in vacuo and the residue dissolved in ethyl acetate (100 mL). The mixture was washed with water (2×75 mL) and brine (75 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography and eluted with a 20% to 40% gradient of ethyl acetate in hexanes to afford tert-butyl (3R)-3-({4-[(5,6-difluoro-2′-oxospiro[1-benzofuran-3,3′-indol]-1′(2′H)-yl)methyl]phenyl}amino)pyrrolidine-1-carboxylate (0.403 g, 74%) as a brown oil: 1H NMR (300 MHz, CDCl3) δ 7.25-7.11 (m, 4H), 7.05-7.00 (m, 1H), 6.89 (d, J=7.7 Hz, 1H), 6.78 (dd, J=10.3, 6.3 Hz, 1H), 6.59 (s, 1H), 6.56 (s, 1H), 6.49 (dd, J=7.9, 7.9 Hz, 1H), 5.02-4.93 (m, 2H), 4.74-4.69 (m, 2H), 4.01 (br s, 1H), 3.76-3.68 (m, 2H), 3.46 (m, 2H), 3.20 (m, 1H), 2.21-2.12 (m, 1H), 1.87 (br s, 1H), 1.46 (s, 9H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 16 h
  3. filtrationfiltered through a pad of diatomaceous earth
  4. concentrationThe filtrate was concentrated in vacuo
  5. dissolutionthe residue dissolved in ethyl acetate (100 mL)
  6. washThe mixture was washed with water (2×75 mL) and brine (75 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by column chromatography
  11. washeluted with a 20% to 40% gradient of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-db13df0498014bd6a26ae919c7578db5
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

Loading…