Formaldehyde → 3-(5-fluoro-2-hydroxyphenyl)-3-(hydroxymethyl)-1-pentyl-1,3-dihydro-2H-indol-2-one

HRID 425478Notes

Reaction equation

[F:1][C:2]1[CH:3]=[CH:4][C:5]([OH:23])=[C:6]([CH:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]([CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[C:9]2=[O:22])[CH:7]=1.[CH2:24]=[O:25].C([N-]C(C)C)(C)C.[Li+].[Cl-].[NH4+]>C1COCC1.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([OH:23])=[C:6]([C:8]2([CH2:24][OH:25])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]([CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[C:9]2=[O:22])[CH:7]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 3-(5-fluoro-2-hydroxyphenyl)-1-pentyl-1,3-dihydro-2H-indol-2-one (2.10 g, 6.70 mmol) in THF (20.0 mL) were added paraformaldehyde (1.76 g, 58.8 mmol) and lithium diisopropylamide (7.35 mL, 2.0 M in THF, 14.7 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 2 hrs followed by the addition of ammonium chloride solution (10.0 mL) and ethyl acetate (100 mL). The organic layer was washed with water and brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo to dryness to give the title compound: 1H NMR (300 MHz, CDCl3) δ 9.55-9.10 (br, 1H), 7.53-6.86 (m, 6H), 6.57-6.49 (m, 1H), 4.74-4.30 (br, 1H), 4.18-4.07 (m, 2H), 3.79-3.60 (m, 2H), 1.77-1.61 (m, 2H), 1.41-1.24 (m, 4H), 0.87 (t, 3H); MS (ES+) m/z 326 (M−17), 366 (M+23).

Workup

washThe organic layer was washed with water and brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationThe filtrate was concentrated in vacuo to dryness

Sources & evidence

ORD record: ord-4ee2ad231d2040f682a16fc031ca4be2
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08106087B2

Reaction notes

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