Ammonia → HCID 11661117, compound

HRID 853846Notes

Reaction equation

HRID 853846 reaction equation
[CH3:1][O:2][CH2:3][C@@H:4]1[CH2:8][CH2:7][CH2:6][N:5]1[S:9]([C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[N:17]([CH2:21][C:22]([CH3:26])([CH3:25])[C:23]#[N:24])[C:16](=O)[C:15]12[O:32]CCCO1)(=[O:11])=[O:10].N>[Ni].CCO>[CH3:1][O:2][CH2:3][C@@H:4]1[CH2:8][CH2:7][CH2:6][N:5]1[S:9]([C:12]1[CH:20]=[CH:19][C:18]2[N:17]3[CH2:21][C:22]([CH3:25])([CH3:26])[CH2:23][N:24]=[C:16]3[C:15](=[O:32])[C:14]=2[CH:13]=1)(=[O:10])=[O:11]

Participants

5

Reactant 2

HCID 222AmmoniaHCID 58932553HCID 58932553, compound

Product 1

HCID 11661117HCID 11661117, compoundYield 103.7%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 702EthanolSolvent

Conditions

Temperature
135 °C

Procedure

3-[5′-{[(2S)-2-(Methoxymethyl)pyrrolidin-1-yl]sulfonyl}-2′-oxospiro[1,3-dioxane-2,3′-indol]-1′ (2′H)-yl]-2,2-dimethylpropanenitrile (1.92 g, 4.14 mmol), wet Raney Nickel (3.59 g), 2M EtOH.NH3 (175 mL) were combined in a Parr Bottle (500 mL) and hydrogenated at 52 lb/in2 H2 for 18 hours. The Raney Nickel was removed by filtration through Sulka Floc and the filter pad was washed well with 2M EtOH.NH3. The filtrate was poured into a steel pressure vessel and heated at 135° C. for 21 hours. The mixture was cooled to room temperature and the solvents were removed. The crude product was purified on Biotage KP silica gel eluting with CH2Cl2/CH3OH/NH4OH (95.5/3/1.5) to give the title compound as a white solid (1.68 g, 90% yield). Anal: Calc'd. for C22H31N3O5S : C, 58.78; H, 6.95; N, 9.35; Found: C, 58.50; H, 7.02; N, 9.22. NMR: consistent. MS; (ES+) m/z 450 [M+H]. IR: consistent. m.p.: 167-169° C. Opt. Rotation: −80.62(calculated) at 25° C. in CH2Cl2 (1% concentration), wavelength 589.

Workup

  1. customfor 18 hours
  2. customThe Raney Nickel was removed by filtration through Sulka Floc
  3. washthe filter pad was washed well with 2M EtOH
  4. additionThe filtrate was poured into a steel pressure vessel
  5. temperatureThe mixture was cooled to room temperature
  6. customthe solvents were removed
  7. customThe crude product was purified on Biotage KP silica gel eluting with CH2Cl2/CH3OH/NH4OH (95.5/3/1.5)

Sources & evidence

ORD record
ord-f3712ee6867b45c7a646d18351938bcf
Source dataset
uspto-grants-2007_08
Patent number
US07256198B2

Reaction notes

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