Propanal → 7-Ethyl-10-Hydroxycamptothecin

HRID 129525

Reaction equation

HRID 129525 reaction equation
[CH3:1][CH2:2][C@@:3]1([OH:27])[C:8](=[O:9])[O:7][CH2:6][C:5]2[C:10]([N:12]3[C:24](=[CH:25][C:4]1=2)[C:23]1[N:22]=[C:21]2[C:16]([CH:17]=[C:18]([OH:26])[CH:19]=[CH:20]2)=[CH:15][C:14]=1[CH2:13]3)=[O:11].[CH:28](=O)[CH2:29]C.S(=O)(=O)(O)O.FC(F)(F)C(O)=O.S(OOS([O-])(=O)=O)([O-])(=O)=O.[K+].[K+]>O.O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Fe+2]>[CH3:28][CH2:29][C:15]1[C:14]2[CH2:13][N:12]3[C:10](=[O:11])[C:5]4[CH2:6][O:7][C:8]([C@:3]([OH:27])([CH2:2][CH3:1])[C:4]=4[CH:25]=[C:24]3[C:23]=2[N:22]=[C:21]2[C:16]=1[CH:17]=[C:18]([OH:26])[CH:19]=[CH:20]2)=[O:9]

Participants

8

Reactant 5

HCID 527PropanalHCID 1118Sulfuric AcidHCID 6422Trifluoroacetic acidHCID 24412Potassium PersulfateHCID 97226Hydroxycamptothecin

Product 1

HCID 1048427-Ethyl-10-Hydroxycamptothecin

Reagents, catalysts & solvents 2

HCID 62662Ferrous sulfate heptahydrateCatalystHCID 962WaterSolvent2×

Procedure

The 10-hydroxy camptothecin (800 mg; 2.2 mmol) is suspended in water (24 ml). Iron (II) sulfate heptahydrate (250 mg, 0.85 millimoles) is added to the suspension and then followed by the addition of propionaldehyde (3 ml). The reaction mixture is then cooled in an ice bath and concentrated sulfuric acid (1 ml) and trifluoroacetic acid (24 ml) are added. After stirring the homogeneous solution for 15 minutes, potassium persulfate (3.5 g; 6 mol equivalent) is added, and the mixture is slowly warmed to room temperature. After approximately 15 hours, the reaction mixture is diluted with water and the product is extracted using excess chloroform. The crude product is washed thrice with 5% methanol in ether and dried to obtain 806 mg of the desired compound. 1H NMR (300 MHz; DMSO-d6): 0.87 δ (3H, t, J=7 Hz); 1.62 δ (3H, t, J=7 Hz); 1.85 δ (2H, 1q, J=5 Hz); 3.18 δ (2H, q, J=5 Hz); 5.19 δ (2H, m); 5.40 δ (2H, s); 6.51 δ (1H, bs); 7.23 δ (2H, m); 7.39 δ (1H, d, J=10 Hz); 8.01 δ (1H, d, J=9Hz) 13C NMR: δ7.3, 13.6, 22.4, 29.8, 72.0, 95.8, 102.7, 117.9, 120.4, 124.8, 144.6, 145.3, 156.5, 158.3, 200.1 FAB MS: 403 (M+1)+

Workup

  1. temperatureThe reaction mixture is then cooled in an ice bath
  2. waitAfter approximately 15 hours
  3. extractionthe product is extracted
  4. washThe crude product is washed thrice with 5% methanol in ether
  5. customdried

Sources & evidence

ORD record
ord-90c9690576e740ad9fcb27059b249382
Source dataset
uspto-grants-1995_11
Patent number
US05468754

Linked notes

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