Acetone → HCID 68752581, compound

HRID 333301Notes

Reaction equation

HRID 333301 reaction equation
[C:1]1([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@H:8]([NH:13][C:14]([C:16]2(CC(Cl)=C)[CH2:20][CH2:19][CH2:18][CH2:17]2)=[O:15])[C:9]([NH:11][CH3:12])=[O:10])=[CH:3][CH:2]=1.[O:31]=[O+][O-].C[C:35]([CH3:37])=[O:36]>>[C:1]1([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@H:8]([NH:13][C:14]([C:16]2([CH2:37][C:35]([OH:31])=[O:36])[CH2:20][CH2:19][CH2:18][CH2:17]2)=[O:15])[C:9]([NH:11][CH3:12])=[O:10])=[CH:3][CH:2]=1

Participants

4

Reactant 3

HCID 180AcetoneHCID 24823OzoneHCID 86665066HCID 86665066, compound

Product 1

HCID 68752581HCID 68752581, compound

Conditions

Temperature
-78 °C

Procedure

To a solution of (S)—N-(3-(biphenyl-4-yl)-1-(methylamino)-1-oxopropan-2-yl)-1-(2-chloroallyl)cyclopentanecarboxamide (38 mg, 0.09 mmol) in acetone (5 mL) at −78° C. was bubbled ozone for 1 minute with a persistent pale blue color. The mixture was stirred at −78° C. for 5 minutes. To the mixture was bubbled oxygen for 10 minutes then added dimethyl sulfide (0.5 mL) followed by 1 mL of water. The mixture was stirred for 1 hr at room temperature and concentrated under reduced pressure. The obtained mixture was diluted in EtOAc and acidified with 1 M HCl. The organic layer was washed with water, brine, dried over MgSO4, filtered and concentrated under reduced pressure. The obtained residue was purified with RP-HPLC (SunFire C8, H2O (0.1% TFA)/CH3CN) to give (S)-2-(1-(3-(biphenyl-4-yl)-1-(methylamino)-1-oxopropan-2-ylcarbamoyl)cyclopentyl)acetic acid (27 mg). HPLC retention time=1.44 minutes (condition B); MS (m+1)=409.0; 1H NMR (400 MHz, ACETONITRILE-d3) δ ppm 1.33-1.63 (m, 6H), 1.72-1.94 (m, 2H), 2.60 (d, J=16.4 Hz, 1H), 2.73 (d, J=4.8 Hz, 3H), 2.73 (d, J=16.4 Hz, 1H), 2.97 (dd, J=14.1, 10.4 Hz, 1H), 3.39 (dd, J=14.1, 4.5 Hz, 1H), 4.58-4.76 (m, 1H), 6.70 (d, J=7.6 Hz, 1H), 7.09 (br. s., 1H), 7.34 (d, J=8.3 Hz, 2H), 7.38 (t, J=7.3 Hz, 1H), 7.43-7.51 (m, 2H), 7.59 (d, J=8.1 Hz, 2H), 7.62-7.67 (m, 2H).

Workup

  1. customTo the mixture was bubbled oxygen for 10 minutes
  2. stirringThe mixture was stirred for 1 hr at room temperature
  3. concentrationconcentrated under reduced pressure
  4. additionThe obtained mixture was diluted in EtOAc
  5. washThe organic layer was washed with water, brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe obtained residue was purified with RP-HPLC (SunFire C8, H2O (0.1% TFA)/CH3CN)

Sources & evidence

ORD record
ord-23743961d8064651b65a6358f50a36c8
Source dataset
uspto-grants-2014_11
Patent number
US08877815B2

Reaction notes

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