Sodium hydride → HCID 59352425, compound

HRID 1407829Notes

Reaction equation

HRID 1407829 reaction equation
[O:1]=[C:2]1[C:10]2([C:14]3[CH:15]=[CH:16][C:17]([O:19][CH:20]4[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21]4)=[CH:18][C:13]=3[O:12][CH2:11]2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[NH:3]1.[H-].[Na+].Br[CH2:35][C:36]1[O:37][C:38]([C:41]([F:44])([F:43])[F:42])=[CH:39][CH:40]=1>CN(C)C=O>[O:1]=[C:2]1[C:10]2([C:14]3[CH:15]=[CH:16][C:17]([O:19][CH:20]4[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21]4)=[CH:18][C:13]=3[O:12][CH2:11]2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]1[CH2:35][C:36]1[O:37][C:38]([C:41]([F:44])([F:43])[F:42])=[CH:39][CH:40]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27946052-(Bromomethyl)-5-(trifluoromethyl)furanHCID 67356302HCID 67356302, compound

Product 1

HCID 59352425HCID 59352425, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of tert-butyl 3-[(2′-oxo-1,2′-dihydrospiro[1-benzofuran-3,3-indol]-6-yl)oxy]pyrrolidine-1-carboxylate (0.19 g, 0.45 mol) in N,N-dimethyl formamide (10 mL) was added sodium hydride (0.02 g, 0.54 mmol) slowly at 0° C. After 30 min, 2-(bromomethyl)-5-(trifluoromethyl)furan (0.12 g, 0.54 mmol) was added. The mixture was stirred at ambient temperature for 16 h, and then quenched with saturated ammonium chloride (10 mL). The mixture was extracted with ethyl acetate (3×20 mL). The combined organic solution was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was subjected to column chromatography (ethyl acetate/hexanes, 1/2) to afford tert-butyl 3-[(2′-oxo-1′-{[5-(trifluoromethyl)furan-2-yl]methyl}-1′,2′-dihydrospiro[1-benzofuran-3,3-indol]-6-yl)oxy]pyrrolidine-1-carboxylate (0.14 g, 55%) as a colorless solid: 1H NMR (300 MHz, CDCl3) δ7.29 (t, J=7.7 Hz, 1H), 7.16 (d, J=7.4 Hz, 1H), 7.06 (t, J=7.5 Hz, 1H), 6.97 (d, J=7.8 Hz, 1H), 6.76-6.70 (m, 1H), 6.54 (d, J=8.2 Hz, 1H), 6.47 (s, 1H), 6.40-6.35 (m, 1H), 6.30 (d, J=8.2 Hz, 1H), 5.06 (d, J=16.2 Hz, 1H), 4.95 (d, J=9.0 Hz, 1H), 4.86 (d, J=16.2 Hz, 1H), 4.80 (br s, 1H), 4.69 (d, J=9.0 Hz, 1H), 3.64-3.37 (m, 4H), 2.22-1.96 (m, 2H), 1.45 (s, 9H); MS (ES+) m/z 593.2 (M+23).

Workup

  1. customquenched with saturated ammonium chloride (10 mL)
  2. extractionThe mixture was extracted with ethyl acetate (3×20 mL)
  3. dry with materialThe combined organic solution was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-453e0a4f58e9452fab5a98dfcfb4f59d
Source dataset
uspto-grants-2014_12
Patent number
US08916580B2

Reaction notes

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