Hydrochloric Acid → 5-[[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethoxy)phenyl](ethyl)amino]pentanoic acid

HRID 505293Notes

Reaction equation

HRID 505293 reaction equation
[F:1][C:2]([F:42])([F:41])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([O:26][C:27]([F:30])([F:29])[F:28])[CH:23]=[CH:22][C:21]=3[N:31]([CH2:38][CH3:39])[CH2:32][CH2:33][CH2:34][CH2:35][CH:36]=[O:37])[C@H:14]2[CH3:40])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.CC(=CC)C.[O-:48]Cl=O.[Na+].Cl>C1COCC1.CC(O)(C)C.O.CCOC(C)=O>[F:42][C:2]([F:1])([F:41])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([O:26][C:27]([F:28])([F:29])[F:30])[CH:23]=[CH:22][C:21]=3[N:31]([CH2:38][CH3:39])[CH2:32][CH2:33][CH2:34][CH2:35][C:36]([OH:48])=[O:37])[C@H:14]2[CH3:40])[CH:6]=[C:7]([C:9]([F:11])([F:10])[F:12])[CH:8]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 105532-Methyl-2-buteneHCID 23668197Sodium ChloriteHCID 248965325-[[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethoxy)phenyl](ethyl)amino]pentanal

Product 1

HCID 248965335-[[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethoxy)phenyl](ethyl)amino]pentanoic acid

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 6386tert-ButanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-[[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethoxy)phenyl](ethyl)amino]pentanal (6.8 mg, 0.011 mmol) in THF (20 μL) and t-BuOH (60 μL) was added 2-methyl-2-butene (20 μL), followed by a solution of NaClO2 (3.0 mg, 0.024 mmol) and NaH2PO4 (3.5 mg, 0.024 mmol) in water (25 μL). The reaction was stirred at room temperature for 30 minutes and then diluted with EtOAc (8 mL) and water (2 mL), acidified with 1 N HCl (2 mL), and washed with brine (5 mL). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue by PTLC (EtOAc) afforded 5-[[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethoxy)phenyl](ethyl)amino]pentanoic acid. Rf=0.20 (EtOAc). LCMS=631.3 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 7.88 (s, 1H), 7.78 (s, 2H), 7.18-7.15 (m, 3H), 5.73 (d, J=8.0 Hz, 1H), 4.75 (d, J=16.5 Hz, 1H), 4.58 (m, 1H), 4.03 (s, 1H), 2.97 (m, 4H), 2.31 (t, J=7.3 Hz, 2H), 1.40-1.23 (m, 5H), 1.00 (t, J=6.7 Hz, 3H), 0.69 (d, J=6.4 Hz, 3H).

Workup

  1. washwashed with brine (5 mL)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification of the residue by PTLC (EtOAc)

Sources & evidence

ORD record
ord-bf61750d642742159ccdf7eb357c6cfd
Source dataset
uspto-grants-2010_08
Patent number
US07781426B2

Reaction notes

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