Hydrogen Peroxide → HCID 58592902, compound

HRID 1518960Notes

Reaction equation

HRID 1518960 reaction equation
[C:1]1([C:7]2[CH2:12][N:11]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:10][CH2:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-:20].[Na+].OO>C1COCC1.O.CCOC(C)=O>[OH:20][C@@H:8]1[CH2:9][CH2:10][N:11]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:12][C@H:7]1[C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

7

Reactant 3

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 57440164HCID 57440164, compound

Product 1

HCID 58592902HCID 58592902, compoundYield 77.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
22 °C

Procedure

Add slowly over 35 minutes a 1M solution of borane tetrahydrofuran complex (137.35 mmol; 137.35 mL) to a solution of tert-butyl 5-phenyl-3,6-dihydro-2H-pyridine-1-carboxylate (137.35 mmol; 36.20 g) in anhydrous THF (362.00) at 0° C. under nitrogen and warm the mixture to 22° C. for 18 h. Then, add slowly a 2M aqueous solution of NaOH (54.94 mmol; 27.47 mL) at 0° C. and stir the mixture for 5 min. Add a 35% aqueous solution of hydrogen peroxide (274.70 mmol; 23.88 mL) at 0° C. and stir the mixture at 22° C. for 2 h, dilute with water (300 mL). Dilute the mixture with EtOAc (250 mL) and separate the organic layer. Extract the aqueous layer with EtOAc (250 mL). Wash the combined organic layers with sodium bisulfate (214.39 mL) and concentrate. Purify the residue by flash chromatography (750 g column; eluent:hexane/EtOAc 80:20 to 60:40; 400 mL fractions, charge in DCM (100 mL)) and then by chiral chromatography Chiralpak AD, 20 um, 8×25 cm; mobile phase: Isocratic 100% MeOH-0.2% DMEA Flow rate: 300 ml/min UV detection: 225 nm Loading: 3 g/6 min. Collect the first eluting isomer to give the title compound (11.85 g, 31%). MS (m/z): 222 (M-tBu+1) [Alpha]Na=−22.89 (in methanol, 25° C.)

Workup

  1. stirringstir the mixture at 22° C. for 2 h
  2. customseparate the organic layer
  3. extractionExtract the aqueous layer with EtOAc (250 mL)
  4. washWash the combined organic layers with sodium bisulfate (214.39 mL)
  5. concentrationconcentrate
  6. customPurify the residue
  7. additionby flash chromatography (750 g column; eluent:hexane/EtOAc 80:20 to 60:40; 400 mL fractions, charge in DCM (100 mL))
  8. custom3 g/6 min
  9. customCollect the first eluting isomer

Sources & evidence

ORD record
ord-931f091fed1842a2b476ce685579d26a
Source dataset
uspto-grants-2015_07
Patent number
US09073856B2

Reaction notes

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