HCID 57871277, compound → HCID 57871291, compound

HRID 332133Notes

Reaction equation

HRID 332133 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]2[C:10]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[C:16]([Cl:21])[CH:15]=3)([CH2:11]2)[C:9]1=[O:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li][CH3:24]>CCOCC.C1COCC1>[C:1]([O:5][C:6](=[O:7])[NH:8][CH2:13][CH:12]1[CH2:11][C:10]1([C:9](=[O:22])[CH3:24])[C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[C:16]([Cl:21])[CH:15]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 57871277HCID 57871277, compoundHCID 178418348HCID 178418348, compound

Product 1

HCID 57871291HCID 57871291, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a flame-dried, 10 mL round-bottomed flask was added a solution of 1-(3,4-dichlorophenyl)-2-oxo-3-azabicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester in 2 mL of ether and 1.0 mL of THF under Ar (g). The solution was cooled in a dry ice/acetone bath with stirring. A solution of MeLi was added drop-wise and the resulting orange colored mixture was stirred at −78° C. for 3 hours. The solution was warmed to ambient temperature and quenched with 15 mL of 1N HCl. The organic layer was extracted with EtOAc (2×20 mL) and the combined layers washed with brine (20 mL). The organic layer was dried over sodium sulfate for 2 hours and filtered, concentrated under reduced pressure, and dried for 1 hour to afford 1.1 g of a brown oil. The oil was purified on a filter pad of silica eluting with 100/1 (v/v) CHCl3/MeOH. The desired fractions were collected, concentrated under reduced pressure, and dried to afford a yellow oil. Yield: 0.659 g 52%; 1H NMR (300 MHz, CDCl3) δ□7.46 (d, 1H, J=2.1 Hz, ArH), 7.39 (d, 1H, J=5.4 Hz, ArH), 7.20 (dd, 1H, J=5.4, 2.1 Hz, ArH), 4.73 (m, 1H, NH), 3.41 (m, 1H, CH2N), 3.15 (m, 1H, CH2N), 2.04 (s, 3H, CH3), 1.80 (m, CHCH2N), 1.45-1.58 (m, 9H, tert-Bu), 1.20 (dd, 2H, J=4.5 Hz, ArCCH2).

Workup

  1. temperatureThe solution was cooled in a dry ice/acetone bath
  2. stirringthe resulting orange colored mixture was stirred at −78° C. for 3 hours
  3. customquenched with 15 mL of 1N HCl
  4. extractionThe organic layer was extracted with EtOAc (2×20 mL)
  5. washthe combined layers washed with brine (20 mL)
  6. dry with materialThe organic layer was dried over sodium sulfate for 2 hours
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customdried for 1 hour

Sources & evidence

ORD record
ord-e963e4e41865476faaba1280c3fd2d8e
Source dataset
uspto-grants-2014_11
Patent number
US08877798B2

Reaction notes

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