Sodium Iodide → Tert-butyl 3-((1-(4-fluorophenyl)-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate

HRID 1751093Notes

Reaction equation

HRID 1751093 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3([CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)[C:11](=[O:18])[N:10]([CH2:19][C:20]3[CH:21]=[C:22]([CH:30]=[CH:31][CH:32]=3)[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:9]2)=[CH:4][CH:3]=1.Cl[CH2:34][CH2:35][CH2:36][C:37]([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)=[O:38].[I-].[Na+].C(=O)([O-])[O-].[K+].[K+]>CC(=O)CC>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:12]3([CH2:13][CH2:14][N:15]([CH2:34][CH2:35][CH2:36][C:37](=[O:38])[C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)[CH2:16][CH2:17]3)[C:11](=[O:18])[N:10]([CH2:19][C:20]3[CH:21]=[C:22]([CH:30]=[CH:31][CH:32]=3)[C:23]([O:25][C:26]([CH3:27])([CH3:28])[CH3:29])=[O:24])[CH2:9]2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 2535334-ChlorobutyrophenoneHCID 66652535Tert-butyl 3-((1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate

Product 1

HCID 58046799Tert-butyl 3-((1-(4-fluorophenyl)-4-oxo-8-(4-oxo-4-phenylbutyl)-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoateYield 46%

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent

Conditions

Temperature
81 °C

Procedure

A mixture of tert-butyl 3-((1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate (250 mg, 0.57 mmol, 1 equiv), 4-chloro-1-phenylbutan-1-one (91.3 μl, 0.57 mmol, 1 equiv), sodium iodide (34 mg, 0.23 mmol, 0.4 equiv) and potassium carbonate (158 mg, 1.14 mmol, 2 equiv) in 2-butanone was stirred at 81° C. for 16 h. After cooling, the reaction mixture was filtered, concentrated in vacuo and was purified using the Biotage flash chromatography system (SNAP 10 g cartridge, Rf=0.45, gradient—1%-10% methanol in dichloromethane) to afford the title compound (100 mg, 46%); 1H NMR (400 MHz, DMSO-d6): δ 1.53 (s, 9H); 1.59-1.63 (m, 2H); 1.82 (t, 2H, J=7.2 and 6.4 Hz); 2.19-2.23 (m, 2H); 2.37-2.39 (m, 2H); 2.70 (d, 4H, J=7.2 Hz); 3.02 (t, 2H, J=6.8 and 6.4 Hz); 4.54 (s, 2H); 4.59 (s, 2H); 6.84 (bs, 2H); 7.02 (t, 2H, J=9.6 and 8.8 Hz); 7.48-7.54 (m, 2H); 7.63 (t, 1H, J=8 Hz); 7.79-7.84 (m, 2H); 7.95-7.98 (m, 2H); MS for C35H40FN3O4 m/z 586.5 (M+H)+.

Workup

  1. temperatureAfter cooling
  2. filtrationthe reaction mixture was filtered
  3. concentrationconcentrated in vacuo
  4. customwas purified

Sources & evidence

ORD record
ord-97705d2a92934ebd81c57c201c53477a
Source dataset
uspto-grants-2015_10
Patent number
US09156840B2

Reaction notes

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