Trifluoroacetic acid → (S)-3-((S)-3-(4-(3-Aminobenzyloxy)phenyl)-3-(isoxazol-3-yl)propanoyl)-4-benzyloxazolidin-2-one

HRID 1675260Notes

Reaction equation

HRID 1675260 reaction equation
[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:44])[CH2:15][C@@H:16]([C:22]1[CH:43]=[CH:42][C:25]([O:26][CH2:27][C:28]2[CH:29]=[C:30]([NH:34]C(=O)OC(C)(C)C)[CH:31]=[CH:32][CH:33]=2)=[CH:24][CH:23]=1)[C:17]1[CH:21]=[CH:20][O:19][N:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:34][C:30]1[CH:29]=[C:28]([CH:33]=[CH:32][CH:31]=1)[CH2:27][O:26][C:25]1[CH:42]=[CH:43][C:22]([C@@H:16]([C:17]2[CH:21]=[CH:20][O:19][N:18]=2)[CH2:15][C:14]([N:9]2[C@@H:8]([CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH2:12][O:11][C:10]2=[O:13])=[O:44])=[CH:23][CH:24]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59300702tert-Butyl 3-((4-((S)-3-((S)-4-benzyl-2-oxooxazolidin-3-yl)-1-(isoxazol-3-yl)-3-oxopropyl)phenoxy)methyl)phenylcarbamate

Product 1

HCID 59300664(S)-3-((S)-3-(4-(3-Aminobenzyloxy)phenyl)-3-(isoxazol-3-yl)propanoyl)-4-benzyloxazolidin-2-oneYield 57%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a cooled solution (0° C.) of carbamate 27.2 (430 mg, 0.719 mmol) in DCM (4 mL), was slowly added TFA (4 mL). The reaction mixture was allowed to slowly warm to room temperature over three hours. The mixture was then concentrated to dryness under reduced pressure and dissolved in DCM (100 mL). The resulting mixture was extracted with saturated sodium bicarbonate solution (1×30 mL). The aqueous layer was then extracted with DCM (1×50 mL). The organic layers were then combined and washed with brine (1×50 mL) and dried over magnesium sulfate. The filtrate was concentrated, and the residue was purified by medium pressure chromatography (silica gel, 20 to 60% EtOAc:DCM) to give 27.3 (204 mg). MS ESI (pos.) m/e 498.1 (M+H). 1H NMR (400 MHz, CDCl3) δ ppm 8.21 (1 H, d, J=1.6 Hz), 7.09-7.29 (8 H, m), 6.75-6.88 (4 H, m), 6.68 (1 H, dd, J=7.6, 2.2 Hz), 6.06 (1 H, d, J=1.6 Hz), 4.89 (2 H, s), 4.67 (1 H, dd, J=8.2, 6.7 Hz), 4.50-4.58 (1 H, m), 4.01-4.06 (2 H, m), 3.94 (1 H, dd, J=17.6, 8.6 Hz), 3.42-3.49 (1H, m), 3.13 (1 H, dd, J=13.5, 3.3 Hz), 2.68 (1 H, dd, J=13.5, 9.6 Hz).

Workup

  1. concentrationThe mixture was then concentrated to dryness under reduced pressure
  2. dissolutiondissolved in DCM (100 mL)
  3. extractionThe resulting mixture was extracted with saturated sodium bicarbonate solution (1×30 mL)
  4. extractionThe aqueous layer was then extracted with DCM (1×50 mL)
  5. washwashed with brine (1×50 mL)
  6. dry with materialdried over magnesium sulfate
  7. concentrationThe filtrate was concentrated
  8. customthe residue was purified by medium pressure chromatography (silica gel, 20 to 60% EtOAc:DCM)

Sources & evidence

ORD record
ord-1b375ceb19f24e7fbf1fe3b0aa60851e
Source dataset
uspto-grants-2011_08
Patent number
US08003648B2

Reaction notes

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