Trifluoroacetic acid → 8-(1-Hydroxy-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)propan-2-yl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one

HRID 1501862Notes

Reaction equation

HRID 1501862 reaction equation
[Si]([O:8][CH2:9][CH:10]([N:23]1[CH2:40][CH2:39][C:26]2([C:30](=[O:31])[N:29]([C:32]3[CH2:33][O:34][C:35](=[O:38])[C:36]=3[CH3:37])[CH2:28][CH2:27]2)[CH2:25][CH2:24]1)[CH2:11][C:12]1[C:13]([CH3:22])=[C:14]2[C:18](=[CH:19][CH:20]=1)[C:17](=[O:21])[O:16][CH2:15]2)(C(C)(C)C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[OH:8][CH2:9][CH:10]([N:23]1[CH2:40][CH2:39][C:26]2([C:30](=[O:31])[N:29]([C:32]3[CH2:33][O:34][C:35](=[O:38])[C:36]=3[CH3:37])[CH2:28][CH2:27]2)[CH2:25][CH2:24]1)[CH2:11][C:12]1[C:13]([CH3:22])=[C:14]2[C:18](=[CH:19][CH:20]=1)[C:17](=[O:21])[O:16][CH2:15]2

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 867095348-(1-((Tert-butyldimethylsilyl)oxy)-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)propan-2-yl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one

Product 1

HCID 867095358-(1-Hydroxy-3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)propan-2-yl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 8-(1-((tert-butyldimethylsilyl)oxy)-3-(4-methyl-1-oxo-1,3-dihydro isobenzofuran-5-yl)propan-2-yl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one (0.10 g, 0.18 mmol) in DCM (3 mL) was added trifluoroacetic acid (3 mL) at 0° C. After stirring at room temperature for 24 h, solvent was removed under reduced pressure and the residue was purified by preparative-HPLC to give the title compound, which was separated by SFC chiral chromatography into two single enantiomers Isomer A (faster eluting) and Isomer B (slower eluting. Column: CHIRALPAK AD 250×30 mm I.D., 20 μm; Mobile phase: Supercritical CO2EtOH (0.2% NH3H2O)=45/55; Flow rate: 80 ml/min. For both isomers: LC-MS (ESI, m/z): 455 [M+1]+.

Workup

  1. customsolvent was removed under reduced pressure
  2. customthe residue was purified by preparative-HPLC

Sources & evidence

ORD record
ord-871b495c4fc4409ba4e9b9a82ebc3a0a
Source dataset
uspto-grants-2015_12
Patent number
US09206198B2

Reaction notes

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