Ozone → HCID 59607865, compound

HRID 70858Notes

Reaction equation

HRID 70858 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][C@@H:15]([NH:20][C:21]([C:23]3[O:27][C:26]([C:28](C)=[CH2:29])=[N:25][CH:24]=3)=[O:22])[CH2:16][C:17]([OH:19])=[O:18])=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[O:31]=[O+][O-]>C(Cl)Cl.CO>[C:28]([C:26]1[O:27][C:23]([C:21]([NH:20][C@H:15]([CH2:14][C:11]2[CH:10]=[CH:9][C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=3)=[CH:13][CH:12]=2)[CH2:16][C:17]([OH:19])=[O:18])=[O:22])=[CH:24][N:25]=1)(=[O:31])[CH3:29]

Participants

5

Reactant 2

HCID 24823OzoneHCID 59607567HCID 59607567, compound

Product 1

HCID 59607865HCID 59607865, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-4-(3′-chlorobiphenyl-4-yl)-3-(2-(prop-1-en-2-yl)oxazole-5-carboxamido)butanoic acid (60 mg, 0.14 mmol) in DCM (2 mL) and MeOH (2 mL) at −78° C. is bubbled ozone for 30 seconds. After 30 seconds ozone is removed and oxygen is bubbled for 10 minutes. After bubbling oxygen for 10 minutes the −78° C. bath is removed and the reaction is quenched with polymer supported triphenylphosphine and the reaction is stirred at room temperature for 2 hours. After 2 hours the reaction is filtered to remove triphenylphosphineoxide on supported polymer and the filtrate is collected and concentrated under reduced pressure. The obtained residue is purified by RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN), and then lyophilized to give (R)-3-(2-acetyloxazole-5-carboxamido)-4-(3′-chlorobiphenyl-4-yl)butanoic acid (13 mg). HPLC retention time=1.67 minutes (condition D); MS (m+1)=427.0; 1H NMR (400 MHz, DMSO-d6) δ ppm 2.53-2.59 (m, 2 H) 2.60 (s, 3 H) 2.87 (dd, J=10.9, 3.3 Hz, 1 H) 2.94 (dd, J=10.9, 5.1 Hz, 1 H) 4.46-4.60 (m, 1 H) 7.31 (d, J=8.1 Hz, 2 H) 7.36-7.43 (m, 1 H) 7.47 (t, J=7.8 Hz, 1 H) 7.62 (d, J=8.3 Hz, 3 H) 7.69 (t, J=1.9 Hz, 1 H) 7.94 (s, 1 H) 8.86 (d, J=8.6 Hz, 1 H) 12.31 (br. s., 1 H).

Workup

  1. customAfter 30 seconds ozone is removed
  2. customoxygen is bubbled for 10 minutes
  3. customAfter bubbling oxygen for 10 minutes the −78° C. bath
  4. customis removed
  5. customthe reaction is quenched with polymer
  6. filtrationAfter 2 hours the reaction is filtered
  7. customto remove triphenylphosphineoxide
  8. customthe filtrate is collected
  9. concentrationconcentrated under reduced pressure
  10. customThe obtained residue is purified by RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN)

Sources & evidence

ORD record
ord-36b1c45861fd467b9cd8573952c821cc
Source dataset
uspto-grants-2014_09
Patent number
US08822534B2

Reaction notes

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