Acetone → 7'-fluoro-1'-[(1-isopropylpiperidin-4-yl)methyl]spiro[furo[2,3-f][1,3]benzodioxole-7,3'-indol]-2'(1'H)-one

HRID 425663Notes

Reaction equation

HRID 425663 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([CH2:11][CH:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1)[C:8](=[O:18])[C:7]12[C:22]2=[CH:23][C:24]3[O:28][CH2:27][O:26][C:25]=3[CH:29]=[C:21]2[O:20][CH2:19]1.C(N(CC)CC)C.[CH3:37][C:38]([CH3:40])=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([CH2:11][CH:12]1[CH2:17][CH2:16][N:15]([CH:38]([CH3:40])[CH3:37])[CH2:14][CH2:13]1)[C:8](=[O:18])[C:7]12[C:22]2=[CH:23][C:24]3[O:28][CH2:27][O:26][C:25]=3[CH:29]=[C:21]2[O:20][CH2:19]1

Participants

6

Reactant 4

HCID 180AcetoneHCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 666426157'-fluoro-1'-(piperidin-4-ylmethyl)spiro[furo[2,3-f][1,3]benzodioxole-7,3'-indol]-2'(1H)-one

Product 1

HCID 592635187'-fluoro-1'-[(1-isopropylpiperidin-4-yl)methyl]spiro[furo[2,3-f][1,3]benzodioxole-7,3'-indol]-2'(1'H)-oneYield 69.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 7′-fluoro-1′-(piperidin-4-ylmethyl)spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1H)-one (120 mg, 0.28 mmol) and triethylamine (3.9 μL, 0.028 mmol) in 5.00 mL dichloromethane was added acetone (4.1 μL, 0.56 mmol) followed with sodium triacetoxyborohydride (124 mg, 0.56 mmol) at ambient temperature. The mixture was stirred at ambient temperature overnight, quenched with water (10.0 mL). The mixture was extracted with dichloromethane (3×30.0 mL). The combined organic layers was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was subjected to column chromatography (2% methanol in ethyl acetate/hexane) to give 7′-fluoro-1′-[(1-isopropylpiperidin-4-yl)methyl]spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one (85 mg, 69%) as a white solid, which was treated with 2.0 M HCl in diethyl ether to give the title compound: mp 157-160° C.; 1H NMR (300 MHz, CD3OD) δ 7.22-7.05 (m, 2H), 7.05-6.98 (m, 1H), 6.52 (s, 1H), 6.21 (s, 1H), 5.86 (s, 2H), 4.83 (d, 1H), 4.68 (d, 1H), 3.95-3.77 (m, 2H), 3.55-3.42 (m, 3H), 3.12-2.96 (m, 2H), 2.30-2.10 (m, 1H), 2.10-1.97 (m, 2H), 1.76-1.52 (m, 2H), 1.34 (d, 6H); 13C NMR (75 MHz, CD3OD) δ 179.7, 157.6, 150.6, 150.4, 147.1, 143.9, 136.6, 125.8, 121.2, 120.3, 118.0, 103.9, 103.0, 94.3, 81.8, 60.1, 59.7, 47.6, 35.33, 35.30, 28.6, 28.5, 16.98, 16.96; MS (ES+) m/z 439.27 (M+1).

Workup

  1. customquenched with water (10.0 mL)
  2. extractionThe mixture was extracted with dichloromethane (3×30.0 mL)
  3. dry with materialThe combined organic layers was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-4a2c70bb422c48fc862234a0984d69cc
Source dataset
uspto-grants-2012_01
Patent number
US08106087B2

Reaction notes

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