Hydrogen Bromide → HCID 59263438, compound

HRID 1259750Notes

Reaction equation

HRID 1259750 reaction equation
[CH3:1][C:2]1([CH3:37])[CH2:6][O:5][C:4]2=[CH:7][C:8]3[O:9][CH2:10][C:11]4([C:35]=3[CH:36]=[C:3]12)[C:19]1[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=1)[N:13]([CH2:20][CH:21]1[CH2:26][CH2:25][N:24](C(OC(C)(C)C)=O)[CH2:23][CH2:22]1)[C:12]4=[O:34].Br>ClCCl>[CH3:1][C:2]1([CH3:37])[CH2:6][O:5][C:4]2=[CH:7][C:8]3[O:9][CH2:10][C:11]4([C:35]=3[CH:36]=[C:3]12)[C:19]1[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=1)[N:13]([CH2:20][CH:21]1[CH2:22][CH2:23][NH:24][CH2:25][CH2:26]1)[C:12]4=[O:34]

Participants

4

Reactant 2

HCID 260Hydrogen BromideHCID 59263352HCID 59263352, compound

Product 1

HCID 59263438HCID 59263438, compoundYield 46.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of tert-butyl 4-[(5,5-dimethyl-2′-oxo-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-1′(2′H)-yl)methyl]piperidine-1-carboxylate (80 mg, 0.16 m mol) in 10.0 mL dichloromethane was added hydrobromic acid (0.50 mL of hydrobromic acid ≧33% in glacial acetic acid, 1.60 mmol) slowly at 0° C. The mixture was stirred at ambient temperature for one hour and concentrated in vacuo to dryness. The residue was treated with 10.0 mL of 2 N sodium hydroxide solution and extracted with dichloromethane (3×30.0 mL). The combined organic layers was washed with brine (100 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The residue was subjected to column chromatography (2% methanol in ethyl acetate) to give 5,5-dimethyl-1′-(piperidin-4-ylmethyl)-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2′(1′H)-one (0.03 g, 46%), which was treated with 2.0 M HCl in diethyl ether to give the title compound: 1H NMR (300 MHz, CD3OD) δ 7.41 (td, 1H), 7.25-7.12 (m, 3H), 6.43 (s, 1H), 6.37 (s, 1H), 4.87 (d, 1H), 4.72 (d, 1H), 4.23 (s, 2H), 3.80 (d, 2H), 3.51-3.38 (m, 2H), 3.11-2.94 (m, 2H), 2.39-2.19 (m, 1H), 2.06-1.94 (m, 2H), 1.67-1.49 (m, 2H), 1.22 (s, 3H), 1.19 (s, 3H); 13C NMR (75 MHz, CD3OD) δ 181.4, 163.9, 163.4, 144.7, 134.7, 132.3, 131.0, 125.9, 125.8, 122.6, 118.4, 111.3, 94.9, 87.4, 82.6, 60.2, 46.7, 45.7, 45.6, 43.3, 34.6, 28.8, 28.7, 28.6; MS (ES+) m/z 405.4 (M+1).

Workup

  1. concentrationconcentrated in vacuo to dryness
  2. additionThe residue was treated with 10.0 mL of 2 N sodium hydroxide solution
  3. extractionextracted with dichloromethane (3×30.0 mL)
  4. washThe combined organic layers was washed with brine (100 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo to dryness

Sources & evidence

ORD record
ord-a0a2a6d547754f11bc02d376f5d18efe
Source dataset
uspto-grants-2013_06
Patent number
US08466188B2

Reaction notes

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