Ethanol → HCID 58815870, compound

HRID 2245885Notes

Reaction equation

HRID 2245885 reaction equation
[CH2:1]([N:4]1[C@H:9]([CH3:10])[CH2:8][N:7]([C@@H:11]([C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([OH:36])[CH:31]=2)[C:12]2[CH:13]=[C:14]([C:18]([N:20]3[CH2:29][CH2:28][C:23]4(OCC[O:24]4)[CH2:22][CH2:21]3)=[O:19])[CH:15]=[CH:16][CH:17]=2)[C@@H:6]([CH3:37])[CH2:5]1)[CH:2]=[CH2:3].C(O)C.S(=O)(=O)(O)O>ClCCl.C(OCC)(=O)C>[OH-:19].[NH4+:4].[CH2:1]([N:4]1[C@H:9]([CH3:10])[CH2:8][N:7]([C@@H:11]([C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([OH:36])[CH:31]=2)[C:12]2[CH:13]=[C:14]([CH:15]=[CH:16][CH:17]=2)[C:18]([N:20]2[CH2:29][CH2:28][C:23](=[O:24])[CH2:22][CH2:21]2)=[O:19])[C@@H:6]([CH3:37])[CH2:5]1)[CH:2]=[CH2:3]

Participants

6

Reactant 3

HCID 702EthanolHCID 1118Sulfuric AcidHCID 58815957HCID 58815957, compound

Product 2

HCID 14923Ammonium HydroxideYield 2%HCID 58815870HCID 58815870, compoundYield 162.1%

Reagents, catalysts & solvents 1

HCID 21226138Dichloromethane ethylacetateSolvent

Procedure

The ketal of the preceding product, Example 135, was hydrolyzed as follows. A 500 mL round bottom flask equipped with a magnetic stir bar was charged with 21.40 g (40.9 mmol) of {3-[(R)-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)(3-hydroxy-phenyl)methyl]phenyl}-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)methanone, 180 mL ethanol, and 60 mL 10 N aqueous sulfuric acid. The reaction was stirred at room temperature for 20 hours and concentrated under reduced pressure. The residue was partitioned between 150 mL dichloromethane and water, and the aqueous solution was adjusted to pH=8-9 using 50% aqueous NaOH. The layers were separated and the aqueous phase was washed with dichloromethane (2×30 mL). The combined organic extracts were dried over sodium sulfate/magnesium sulfate and the solvent was removed in vacuo, leaving 20.25 g of crude product as a light yellow, viscous oil. Chromatography of this material on ˜100 g of silica gel eluting with dichloromethane/ethyl acetate with 2% ammonium hydroxide yielded 15.30 g (81%) of 1-{3-[(R)-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)(3-hydroxyphenyl)-methyl]-benzoyl}-4-piperidinone as an off-white solid. This material contained 12-13% (as estimated by NMR) of the starting ketal, and was difficult to purify further without significant loss of material. 1H NMR (300 MHz, CDCl3): {tilde over (□)}□{tilde over ()}d, J=6.9 Hz, 1H), 7.45 (s, 1H), 7.40-7.32 (m, 2H), 7.10 (t, J=7.8 Hz, 1H), 6.61 (t, J=7.8 Hz, 2H), 6.56 (s, 1H), 5.94-5.81 (m, 1H), 5.21 (d, J=7.8 Hz, 2H), 5.17 (s, 1H), 3.8 (v br s, 4H), 3.42 (dd, J=5.1, 13.5 Hz, 1H), 2.89-2.82 (m, 2H), 2.62-2.38 (m, 7H), 2.13 (dd, J=1, 10 Hz, 1H), 1.93 (dd, J=1, 9.5 Hz, 1H), 1.17 (d, J=5.9 Hz, 3H), 1.00 (d, J=6.1 Hz, 3H).

Workup

  1. customA 500 mL round bottom flask equipped with a magnetic stir bar
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was partitioned between 150 mL dichloromethane and water
  4. customThe layers were separated
  5. washthe aqueous phase was washed with dichloromethane (2×30 mL)
  6. dry with materialThe combined organic extracts were dried over sodium sulfate/magnesium sulfate
  7. customthe solvent was removed in vacuo
  8. customleaving 20.25 g of crude product as a light yellow, viscous oil

Sources & evidence

ORD record
ord-fc1df5f524314242af6fc36675ed5733
Source dataset
uspto-grants-2010_03
Patent number
US07683168B2

Reaction notes

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