m-Chloroperbenzoic acid → (+/-)-6-(3-Methoxy-phenyl)-7-oxa-3-aza-bicyclo[4.1.0]heptane-3-carboxylic acid tert-butyl ester

HRID 60370Notes

Reaction equation

HRID 60370 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=C(Cl)C=C(C(OO)=[O:30])C=1>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C:11]2([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=3)[CH:12]([O:30]2)[CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 70297m-Chloroperbenzoic acidHCID 22729492HCID 22729492, compound

Product 1

HCID 117720401(+/-)-6-(3-Methoxy-phenyl)-7-oxa-3-aza-bicyclo[4.1.0]heptane-3-carboxylic acid tert-butyl esterYield 95%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

4-(3-Methoxy-phenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (2 g, 6.9 mmol) was further purified by flash chromatography (100 DCM on Silicagel) to remove baseline impurities (likely waste palladium from Suzuki reaction), then was dissolved in methylene chloride (28.9 mL, 451 mmol) and treated with m-CPBA 70-75% (70:30, m-chloroperbenzoic acid: 3-chlorobenzoic acid, 2.4 g, 9.7 mmol) at room temperature overnight. The reaction was quenched by treatment with a Na2S2O3 aq solution, followed by sat. NaHCO3 aq. solution, and further extracted twice with dichloromethane. The combined organic extracts were dried (MgSO4) and filtered, and the solvent was evaporated under reduce pressure. The product was used without further purification in the next step: (±)-6-(3-methoxy-phenyl)-7-oxa-3-aza-bicyclo[4.1.0]heptane-3-carboxylic acid tert-butyl ester (2 g, 95% yield). 1H NMR (CDCl3): δ ppm 7.26 (m, 1H), 6.95 (d, J=7.8 Hz, 1H), 6.90 (br. s., 1H), 6.84 (d, J=8.1 Hz, 1H), 3.93-4.19 (m, 1H), 3.81 (s, 3H), 3.53-3.79 (m, 2H), 3.10-3.24 (m, 2H), 2.38-2.51 (m, 1H), 2.17 (br. s., 1H), 1.48 (s, 9H).

Workup

  1. customto remove baseline impurities (likely waste palladium
  2. customfrom Suzuki reaction),
  3. customThe reaction was quenched by treatment with a Na2S2O3 aq solution
  4. extractionfurther extracted twice with dichloromethane
  5. dry with materialThe combined organic extracts were dried (MgSO4)
  6. filtrationfiltered
  7. customthe solvent was evaporated
  8. customThe product was used without further purification in the next step

Sources & evidence

ORD record
ord-0eb17f54edb3431f8b47c4b1f49486a5
Source dataset
uspto-grants-2016_09
Patent number
US09440984B2

Reaction notes

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