Hydroxylamine → HCID 73051765, compound

HRID 530260Notes

Reaction equation

HRID 530260 reaction equation
[CH3:1][CH:2]([N:4]1[C:12](/[CH:13]=[CH:14]/[CH:15]([OH:23])[CH2:16][CH:17]([OH:22])[CH2:18][C:19](O)=[O:20])=[C:11]([C:24]2[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=2)[C:10]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]1=2)[CH3:3].[NH2:31][OH:32].O.CO>C1COCC1>[F:30][C:27]1[CH:28]=[CH:29][C:24]([C:11]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[N:4]([CH:2]([CH3:3])[CH3:1])[C:12]=2/[CH:13]=[CH:14]/[C@@H:15]([OH:23])[CH2:16][C@@H:17]([OH:22])[CH2:18][C:19]([NH:31][OH:32])=[O:20])=[CH:25][CH:26]=1

Participants

6

Reactant 4

HCID 787HydroxylamineHCID 887MethanolHCID 962WaterHCID 5353627(6E)-7-(3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl)-3,5-dihydroxyhept-6-enoic acid

Product 1

HCID 73051765HCID 73051765, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of fluvastatin (100 mg, 0.25 mmol, in the lactone form) in THF (1 mL) was added 50% hydroxylamine in H2O (0.12 mL, 1.91 mmol). The mixture was stirred at ambient temperature for 16 h, and concentrated under reduced pressure. The residue was extracted with CH2Cl2. The organic layer was washed with brine, dried over MgSO4, filtered, concentrated, and purified by flash chromatography (silica gel; CH2Cl2/MeOH/NEt3 (89:1:9 to 5:5:1)) to give fluva-HA (30 mg, 30%). C24H27FN2O4; white foam; TLC (CH2C1-2/MeOH (9:1)) Rf=0.13; 1H NMR (CDCl3, 400 MHz) δ 7.57-7.59 (1H, d, J=8.4 Hz), 7.41-7.44 (3H, m), 7.13-7.19 (3H, m), 6.99-7.03 (1H, t), 6.69-6.73 (1H, d, J=14.8 Hz), 5.74-5.79 (1H, dd, J=16.4 Hz), 4.95 (1H, br s), 4.39-4.42 (1H, m), 4.21-4.24 (1H, m), 2.24-2.25 (2H, m), 1.64-1.73 (6H, m), 1.32-1.36 (2H, m) ppm; ESI-HRMS calcd for C24H28FN2O4: 427.2033. found: m/z 427.2034 [M+H]+.

Workup

  1. concentrationconcentrated under reduced pressure
  2. extractionThe residue was extracted with CH2Cl2
  3. washThe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by flash chromatography (silica gel; CH2Cl2/MeOH/NEt3 (89:1:9 to 5:5:1))
  8. customto give fluva-HA (30 mg, 30%)

Sources & evidence

ORD record
ord-e8271627361f4493b50e3602cbb69a92
Source dataset
uspto-grants-2016_05
Patent number
US09353061B2

Reaction notes

Loading…