Acetone → HCID 59352328, compound

HRID 1965712Notes

Reaction equation

HRID 1965712 reaction equation
[CH3:1][C:2]([CH3:4])=O.Cl.[NH:6]1[CH2:11][CH2:10][CH:9]([CH2:12][N:13]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]3([C:33]4[C:24](=[CH:25][C:26]5[O:31][CH2:30][CH2:29][O:28][C:27]=5[CH:32]=4)[O:23][CH2:22]3)[C:14]2=[O:34])[CH2:8][CH2:7]1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH3:1][CH:2]([N:6]1[CH2:11][CH2:10][CH:9]([CH2:12][N:13]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]3([C:33]4[C:24](=[CH:25][C:26]5[O:31][CH2:30][CH2:29][O:28][C:27]=5[CH:32]=4)[O:23][CH2:22]3)[C:14]2=[O:34])[CH2:8][CH2:7]1)[CH3:4]

Participants

6

Reactant 4

HCID 180AcetoneHCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 68599039HCID 68599039, compound

Product 1

HCID 59352328HCID 59352328, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a mixture of acetone (0.19 mL, 2.5 mmol) and 1,2-dichloroethane (5.0 mL), were added 1′-(piperidin-4-ylmethyl)-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one hydrochloride (0.36 g, 0.84 mmol), triethylamine (0.35 mL, 2.5 mmol) and sodium triacetoxyborohydride (0.534 g, 2.52 mmol). The mixture was stirred at ambient temperature for 16 h and concentrated in vacuo. The residue was purified by column chromatography and eluted with ethyl acetate/methanol/ammonium hydroxide (20/1/0.2) to afford 1′-{[1-(1-methylethyl)piperidin-4-yl]methyl}-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one. To a solution of this compound in methanol (5 mL) was added a 4 M solution of hydrogen chloride in 1,4-dioxane (1.0 mL, 4.0 mmol) and the mixture was stirred at ambient temperature for 30 min and concentrated in vacuo. Sequential trituration of the residue in hexanes and diethyl ether afforded 1′-{[1-(1-methylethyl)piperidin-4-yl]methyl}-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one hydrochloride (0.21 g, 53%) as an off-white solid: mp 213-216° C.; 1H NMR (300 MHz, DMSO-d6) δ10.02-9.80 (br s, 1H), 7.40-7.02 (m, 4H), 6.51 (s, 1H), 6.18 (s, 1H), 4.74 (d, J=9.3 Hz, 1H), 4.62 (d, J=9.3 Hz, 1H), 4.23-4.06 (m, 4H), 3.73-3.21 (m, 4H), 3.00-2.78 (m, 2H), 2.20-1.52 (m, 5H), 1.32-1.12 (m, 7H); 13C NMR (75 MHz, DMSO-d6) δ176.8, 154.7, 144.0, 142.5, 137.7, 131.6, 128.7, 123.5, 122.8, 121.0, 111.1, 109.2, 98.6, 79.7, 64.1, 63.5, 57.1, 56.7, 47.1, 44.2, 32.1, 26.6, 26.4, 16.1; MS (ES+) m/z 435.1 (M+1).

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was purified by column chromatography
  3. washeluted with ethyl acetate/methanol/ammonium hydroxide (20/1/0.2)

Sources & evidence

ORD record
ord-d6f68541cf7340f495380b869d871e13
Source dataset
uspto-grants-2013_04
Patent number
US08415370B2

Reaction notes

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