Diethyl Ether → HCID 86737467, compound

HRID 1660102Notes

Reaction equation

HRID 1660102 reaction equation
[CH3:1][CH:2]1[CH:27]2[O:28][C:26]2([CH3:29])[CH:25]([OH:30])[CH2:24][C:22](=[O:23])[N:21]([CH3:31])[C:14]2=[C:15]([Cl:20])[C:16]([O:18][CH3:19])=[CH:17][C:12](=[CH:13]2)[CH2:11][C:10]([CH3:32])=[CH:9][CH:8]=[CH:7][CH:6]([O:33][CH3:34])[C:5]2([OH:39])[NH:35][C:36]([O:38][CH:3]1[CH2:4]2)=[O:37].[CH:40]1([C:46]([OH:48])=[O:47])[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]1.C1CCC(N=C=NC2CCCCC2)CC1.C(OCC)C>ClCCl.C(OCC)(=O)C>[CH3:1][CH:2]1[CH:27]2[O:28][C:26]2([CH3:29])[CH:25]([OH:30])[CH2:24][C:22](=[O:23])[N:21]([CH3:31])[C:14]2=[C:15]([Cl:20])[C:16]([O:18][CH3:19])=[CH:17][C:12](=[CH:13]2)[CH2:11][C:10]([CH3:32])=[CH:9][CH:8]=[CH:7][CH:6]([O:33][CH3:34])[C:5]2([OH:39])[NH:35][C:36]([O:38][CH:3]1[CH2:4]2)=[O:37].[CH2:42]1[CH2:43][CH2:44][CH2:45][CH:40]([C:46]([O-:48])=[O:47])[CH2:41]1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 7413Cyclohexanecarboxylic acidHCID 10868DicyclohexylcarbodiimideHCID 5358230HCID 5358230, compound

Product 1

HCID 86737467HCID 86737467, compoundYield 19.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixed solution of maytansinol (103.2 mg. 0.183 m mole) and cyclohexanecarboxylic acid (140 mg, 1.094 m moles) in 5 ml of dry dichloromethane was added DCC (267 mg, 1.296 m moles), and after stirring at room temperature for a short while until insolubles began to separate out, DMAP (50.8 mg, 0.416 m mole) was added. The mixture was stirred at room temperature overnight. Then, the insolubles were filtered off, the filtrate washed with 0.5 N-HCl (ca. 10 ml) and saturated aqueous sodium hydrogen carbonate (ca. 10 ml) in that order, and dried over anhydrous sodium sulfate. The solvent was distilled off and the residue was chromatographed on a column of silica gel (75 g.). Elution was carried out with ethyl acetate, the eluate being collected in 16 g. fractions, and fractions No. 14 through No. 30 were pooled and concentrated to remove the solvent, whereupon 59 mg of crude product was obtained. This crude product was dissolved in ethyl acetate, followed by addition of diethyl ether. By the above procedure there was obtained 24.3 mg of maytansinol 3-cyclohexanecarboxylate as crystals melting at 202°-106° C. (decomp.).

Workup

  1. customto separate out
  2. additionDMAP (50.8 mg, 0.416 m mole) was added
  3. stirringThe mixture was stirred at room temperature overnight
  4. filtrationThen, the insolubles were filtered off
  5. washthe filtrate washed with 0.5 N-HCl (ca. 10 ml) and saturated aqueous sodium hydrogen carbonate (ca. 10 ml) in that order
  6. dry with materialdried over anhydrous sodium sulfate
  7. distillationThe solvent was distilled off
  8. customthe residue was chromatographed on a column of silica gel (75 g.)
  9. washElution
  10. customthe eluate being collected in 16 g
  11. concentrationconcentrated
  12. customto remove the solvent
  13. customwhereupon 59 mg of crude product was obtained

Sources & evidence

ORD record
ord-d003a30648be452c9b114696b77ee0c5
Source dataset
uspto-grants-1981_12
Patent number
US04307016

Reaction notes

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