Hydrochloric Acid → HCID 178461688, compound

HRID 1094326Notes

Reaction equation

HRID 1094326 reaction equation
[O:1]=[C:2]([C@@H:8]([C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2[S:18][CH:19]=[C:20]([C:22]([F:25])([F:24])[F:23])[N:21]=2)=[CH:12][CH:11]=1)[CH3:9])[CH2:3][C:4](OC)=[O:5].[OH-].[Na+].Cl.[NH2:29]O.Cl>CO.CO.O>[F:23][C:22]([F:24])([F:25])[C:20]1[N:21]=[C:17]([NH:16][C:13]2[CH:12]=[CH:11][C:10]([C@H:8]([C:2]3[O:1][N:29]=[C:4]([OH:5])[CH:3]=3)[CH3:9])=[CH:15][CH:14]=2)[S:18][CH:19]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2×HCID 443297Hydroxyamine hydrochlorideHCID 86645979HCID 86645979, compound

Product 1

HCID 178461688HCID 178461688, compoundYield 57%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 22242641Methanol--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

To a cooled (−30° C.) solution of the intermediate 7a, methyl (4R)-3-oxo-4-(4-{[4-(trifluoromethyl)-1,3-thiazol-2-yl]amino}phenyl)pentanoate, (372 mg, 1 mmol) in CH3OH (0.5 ml), a solution of NaOH (42 mg, 1.05 mmol) in CH3OH (4 ml) was added by dripping. The resulting mixture was stirred for 10 min, then a mixture of hydroxylamine hydrochloride (133 mg, 2 mmol) and NaOH (83 mg, 2 mmol) in CH3OH/water (4 ml/0.5 ml) was added at the same temperature. After stirring for 2 h at −30° C., the reaction mixture was poured into 37% HCl (1.5 ml) and the resulting mixture was heated at 80° C. for 2 h. After cooling at room temperature and solvents evaporation, the crude was diluted with water and extracted with EtOAc (3×10 ml). The combined organic extracts were dried over anhydrous Na2SO4, evaporated and purified by flash chromatography (n-hexane/EtOAc 8:2; 1% AcOH) to afford pure 5-[(1R)-1-(4-{[4-(trifluoromethyl)-1,3-thiazol-2-yl]amino}phenyl)ethyl]isoxazol-3-ol (10) (202 mg, 0.57 mmol) as a pale yellow solid (57%). [α]D=−40 (c=1.4; CH3OH); 1H-NMR (CDCl3): δ 10.70 (bs, 1H, OH), 9.15 (bs, 1H, NH), 7.40 (d, 2H, J=7 Hz), 7.25 (d, 2H, J=7 Hz), 7.00 (s, 1H), 5.70 (s, 1H), 3.80 (q, 1H, J=7 Hz), 1.55 (d, 3H, J=7 Hz).

Workup

  1. additionwas added at the same temperature
  2. stirringAfter stirring for 2 h at −30° C.
  3. temperatureAfter cooling at room temperature
  4. customsolvents evaporation
  5. additionthe crude was diluted with water
  6. extractionextracted with EtOAc (3×10 ml)
  7. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  8. customevaporated
  9. custompurified by flash chromatography (n-hexane/EtOAc 8:2; 1% AcOH)

Sources & evidence

ORD record
ord-511ac12dbe464a3d8035978fe4ea8600
Source dataset
uspto-grants-2012_03
Patent number
US08133911B2

Reaction notes

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