Hydrochloric Acid → HCID 71450169, compound

HRID 1429759Notes

Reaction equation

HRID 1429759 reaction equation
[CH3:1][CH2:2][C:3]1[CH2:22][N:20]2[CH2:21][C@@H:5]([CH2:6][C@:7]([C:56]([O:58][CH3:59])=[O:57])([C:23]3[CH:24]=[C:25]4[C@:33]56[C@@H:37]7[C@:38]([CH2:53][CH3:54])([C@@H:42]([O:49][C:50]([CH3:52])=[O:51])[C@:43]([OH:48])([C:44]([O:46][CH3:47])=[O:45])[C@@H:32]5[N:31]([CH3:55])[C:26]4=[CH:27][C:28]=3[O:29][CH3:30])[CH:39]=[CH:40][CH2:41][N:36]7[CH2:35][CH2:34]6)[C:8]3[NH:16][C:15]4[CH:14]=[CH:13][C:12]([F:17])=[CH:11][C:10]=4[C:9]=3[CH2:18][CH2:19]2)[CH:4]=1.Cl.C(C[OH:66])(F)(F)F.[BH4-].[Na+]>O.O.O.O.O.O.O.C([O-])(=O)C([O-])=O.[Fe+3].C([O-])(=O)C([O-])=O.C([O-])(=O)C([O-])=O.[Fe+3].CCOC(C)=O.CO.CCN(CC)CC>[CH3:1][CH2:2][C@@:3]1([OH:66])[CH2:22][N:20]2[CH2:21][C@@H:5]([CH2:6][C@:7]([C:56]([O:58][CH3:59])=[O:57])([C:23]3[CH:24]=[C:25]4[C@:33]56[C@@H:37]7[C@:38]([CH2:53][CH3:54])([C@@H:42]([O:49][C:50]([CH3:52])=[O:51])[C@:43]([OH:48])([C:44]([O:46][CH3:47])=[O:45])[C@@H:32]5[N:31]([CH3:55])[C:26]4=[CH:27][C:28]=3[O:29][CH3:30])[CH:39]=[CH:40][CH2:41][N:36]7[CH2:35][CH2:34]6)[C:8]3[NH:16][C:15]4[CH:14]=[CH:13][C:12]([F:17])=[CH:11][C:10]=4[C:9]=3[CH2:18][CH2:19]2)[CH2:4]1

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 64092,2,2-TrifluoroethanolHCID 4311764Sodium borohydrideHCID 71460965HCID 71460965, compound

Product 1

HCID 71450169HCID 71450169, compoundYield 39%

Reagents, catalysts & solvents 5

HCID 57370413Iron(3+) ethanedioate--water (2/3/6)CatalystHCID 887MethanolSolventHCID 962WaterSolvent3×HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of iron(III) oxalate hexahydrate (60.4 mg, 0.125 mmol, 10 equiv) in H2O (50 mL) was stirred 2 hours. The reaction mixture was cooled to 0° C. and air was bubbled through the mixture for 10 minutes. A solution of 10′-fluoroanhydrovinblastine (19a, 10.1 mg, 0.0125 mmol, 1 equiv) in H2O (0.5 mL), aqueous 0.1 N HCl (0.5 mL), and CF3CH2OH (0.1 mL) was transferred by pipette to the mixture and NaBH4 (9.5 mg, 0.25 mmol, 1 equiv) in H2O (1 mL) was added to the mixture at 0° C. The resulting mixture was stirred for 30 minutes before being quenched by addition of 28-30% aqueous NH4OH (10 mL). The mixture was extracted with 10% MeOH in CH2Cl2 and the organic layer was dried over Na2SO4 and concentrated under reduced pressure. PTLC (SiO2, Et3N:MeOH:EtOAc=3:3:97) provided 10′-fluorovinblastine 19b (4.0 mg, 0.0048 mmol, 39%) as a white solid and 10′-fluoroleurosidine (2.7 mg, 0.0033 mmol, 26%).

Workup

  1. customair was bubbled through the mixture for 10 minutes
  2. additionwas added to the mixture at 0° C
  3. stirringThe resulting mixture was stirred for 30 minutes
  4. custombefore being quenched by addition of 28-30% aqueous NH4OH (10 mL)
  5. extractionThe mixture was extracted with 10% MeOH in CH2Cl2
  6. dry with materialthe organic layer was dried over Na2SO4
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c06290736a5247e78075b92ccc647db2
Source dataset
uspto-grants-2015_01
Patent number
US08940754B2

Reaction notes

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