(R)-(+)-1-Boc-3-aminopyrrolidine → tert-butyl (3R)-3-[(2'-oxo-1'-{[5-(trifluoromethyl)furan-2-yl]methyl}-1',2'-dihydrospiro[1-benzofuran-3,3'-indol]-6-yl)amino]pyrrolidine-1-carboxylate

HRID 2385435Notes

Reaction equation

HRID 2385435 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]2[C:8]3([CH2:28][O:29][C:4]=2[CH:3]=1)[C:16]1[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=1)[N:10]([CH2:17][C:18]1[O:19][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:21][CH:22]=1)[C:9]3=[O:27].[C:30]([N:37]1[CH2:41][CH2:40][C@@H:39]([NH2:42])[CH2:38]1)([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31].CC(P(C(C)(C)C)C1C(C2C=CC=CC=2)=CC=CC=1)(C)C.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[O:27]=[C:9]1[C:8]2([C:5]3[CH:6]=[CH:7][C:2]([NH:42][C@@H:39]4[CH2:40][CH2:41][N:37]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:38]4)=[CH:3][C:4]=3[O:29][CH2:28]2)[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[N:10]1[CH2:17][C:18]1[O:19][C:20]([C:23]([F:26])([F:24])[F:25])=[CH:21][CH:22]=1

Participants

7

Reactant 4

HCID 854070(R)-(+)-1-Boc-3-aminopyrrolidineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 461941796-bromo-1'-((5-(trifluoromethyl)furan-2-yl)methyl)-2H-spiro[benzofuran-3,3'-indolin]-2'-one

Product 1

HCID 59352482tert-butyl (3R)-3-[(2'-oxo-1'-{[5-(trifluoromethyl)furan-2-yl]methyl}-1',2'-dihydrospiro[1-benzofuran-3,3'-indol]-6-yl)amino]pyrrolidine-1-carboxylateYield 48%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of 6-bromo-1′-{[5-(trifluoromethyl)furan-2-yl]methyl}spiro[1-benzofuran-3,3′-indol]-2′(1′H)-one (0.80 g, 1.73 mmol), (R)-1-Boc-3-aminopyrrolidine (0.48 g, 2.59 mmol) and (2-biphenyl)di-tert-butylphosphine (0.08 g, 0.28 mmol) in toluene (15 mL) was added palladium(II) acetate (0.09 g, 0.14 mmol) followed by the addition of sodium tert-butoxide (0.42 g, 4.3 mmol). The mixture was stirred at 100° C. for 18 h. The mixture was filtered through a pad of celite, and the filtrate was concentrated in vacuo. The residue was subjected to column chromatography (ethyl acetate/hexane; 1/2) to afford tert-butyl (3R)-3-[(2′-oxo-1′-{[5-(trifluoromethyl)furan-2-yl]methyl}-1′,2′-dihydrospiro[1-benzofuran-3,3′-indol]-6-yl)amino]pyrrolidine-1-carboxylate (0.47 g, 48%): 1H NMR (300 MHz, CDCl3) δ7.32-7.24 (m, 1H), 7.17 (d, J=7.4 Hz, 1H), 7.05 (dd, J=7.4 Hz, 1H), 6.95 (d, J=7.8 Hz, 1H), 6.76-6.69 (m, 1H), 6.45 (d, J=8.2 Hz, 1H), 6.36 (d, J=3.2 Hz, 1H), 6.19 (d, J=2.0 Hz, 1H), 6.02 (dd, J=8.2, 2.0 Hz, 1H), 5.05 (d, J=16.2 Hz, 1H), 4.95-4.81 (m, 2H), 4.65 (d, J=9.0 Hz, 1H), 4.00-3.90 (m, 1H), 3.88-3.76 (m, 1H), 3.73-3.57 (m, 1H), 3.52-3.34 (m, 2H), 3.30-3.11 (m, 1H), 2.23-2.06 (m, 1H), 1.96-1.77 (m, 1H), 1.45 (s, 9H); MS (ES+) m/z 570.2 (M+1).

Workup

  1. filtrationThe mixture was filtered through a pad of celite
  2. concentrationthe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-d7cfc6f56a5441eebecc98516c58537f
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

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