Diethyl Ether → HCID 86737467, compound

HRID 848053Notes

Reaction equation

HRID 848053 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.C1(N=C=NC2CCCCC2)CCCCC1.CCOCC>ClCCl.CN(C)C1C=CN=CC=1.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

8

Reactant 4

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

Product 1

HCID 86737467HCID 86737467, compoundYield 19.2%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixed solution of maytansinol (103.2 mg, 0.183 mmoles) and cyclohexanecarboxylic acid (140 mg, 1.094 mmoles) in 5 ml of dry dichloromethane is added dicyclohexylcarbodiimide (DCC) (267 mg, 1.296 mmoles), and after stirring at a room temperature for a short while until insolubles begin to separate out, p-dimethylaminopyridine (DMAP) (50.8 mg, 0.416 mmoles) is added. The mixture is stirred at a room temperature overnight. Then, the insolubles are filtered off, and the filtrate is washed with 0.5 N-HCl (ca. 10 ml) and with saturated aqueous sodium hydrogen carbonate (ca. 10 ml) in that order and is dried over anhydrous sodium sulfate. The solvent is distilled off, and the residue is chromatographed on a column of silica gel (75 g), followed by eluting with ethyl acetate and collecting the eluate in 16 g fractions. The fractions No. 14 through No. 30 are pooled and concentrated to remove the solvent, resulting in 59 mg of the crude product. The crude product is dissolved in ethyl acetate, followed by adding ether. There is obtained 24.3 mg of maytansinol 3-cyclohexanecarboxylate as crystals melting at 202°-206° C. (decomp.).

Workup

  1. customto separate out
  2. stirringThe mixture is stirred at a room temperature overnight
  3. filtrationThen, the insolubles are filtered off
  4. washthe filtrate is washed with 0.5 N-HCl (ca. 10 ml) and with saturated aqueous sodium hydrogen carbonate (ca. 10 ml) in that order
  5. dry with materialis dried over anhydrous sodium sulfate
  6. distillationThe solvent is distilled off
  7. customthe residue is chromatographed on a column of silica gel (75 g)
  8. washby eluting with ethyl acetate
  9. customcollecting the eluate in 16 g fractions
  10. concentrationconcentrated
  11. customto remove the solvent
  12. customresulting in 59 mg of the crude product

Sources & evidence

ORD record
ord-b8de1bca03504453a768dac3dfd74039
Source dataset
uspto-grants-1981_10
Patent number
US04294757

Reaction notes

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