Ammonia → HCID 11662369, compound

HRID 853858Notes

Reaction equation

HRID 853858 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][CH2:31][CH2:30][CH2:29][O:28]1)(=[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]([CH3:26])([CH3:25])[CH2:23][N:24]=[C:16]3[C:15]3([O:28][CH2:29][CH2:30][CH2:31][O:32]3)[C:14]=2[CH:13]=1)(=[O:10])=[O:11]

Participants

5

Reactant 2

HCID 222AmmoniaHCID 58932543HCID 58932543, compound

Product 1

HCID 11662369HCID 11662369, compound

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 702EthanolSolvent

Conditions

Temperature
135 °C

Procedure

3-[5′-{[(2R)-2-(Methoxymethyl)pyrrolidin-1-yl]sulfonyl}-2′-oxospiro[1,3-dioxane-2,3′-indol]-1′(2′H)-yl]-2,2-dimethylpropanenitrile (1.00 g, 2.16 mmol), wet Raney Nickel (1.16 g) and 2M EtOH.NH3 (100 mL) was hydrogenated in a Parr Bottle (500 mL) at 56 lb/in2 H2 for 18 hours. The Raney nickel was removed by filtration through Sulka Floc. The filtrate was poured into a steel pressure vessel and was heated at 135° C. for 20 hours. The mixture was cooled to room temperature and concentrated. The crude product was purified on Biotage KP silica gel eluting with CH2Cl2/CH3OH/NH4OH (97.75/1.5/0.75) to give the title compound as a white solid. Anal: Calc'd for C22H31N3O5S+0.2M H2O: C, 58.31% ; H, 6.98% ; N, 9.27% . Found: C, 58.10; H, 6.96; N, 9.06. NMR (400 MHz, DMSO-d6): consistent. MS: (ES+) m/z 450 [M+H]. Opt. Rotation: +75.02(calculated) at 25° C. in CH2Cl2 (1% concentration) at 589 wavelength; Analytical HPLC: major component=99.3% at 254 nm; m.p.: 169-171° C.

Workup

  1. customfor 18 hours
  2. customThe Raney nickel was removed by filtration through Sulka Floc
  3. additionThe filtrate was poured into a steel pressure vessel
  4. temperatureThe mixture was cooled to room temperature
  5. concentrationconcentrated
  6. customThe crude product was purified on Biotage KP silica gel eluting with CH2Cl2/CH3OH/NH4OH (97.75/1.5/0.75)

Sources & evidence

ORD record
ord-aaad3dc96aeb4fa98c40896d202bd5a4
Source dataset
uspto-grants-2007_08
Patent number
US07256198B2

Reaction notes

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