Cyclohexanecarboxylic acid → HCID 86737467, compound

HRID 1413103Notes

Reaction equation

HRID 1413103 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>ClCCl.CN(C)C1C=CN=CC=1>[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

6

Reactant 3

HCID 7413Cyclohexanecarboxylic acidHCID 10868DicyclohexylcarbodiimideHCID 5358230HCID 5358230, compound

Product 1

HCID 86737467HCID 86737467, compoundYield 19.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

In 5 ml of dry dichloromethane are dissolved maytansinol (103.2 mg, 0.183 mmol) and cyclohexanecarboxylic acid (140 mg, 1.094 mmols), followed by addition of dicyclohexylcarbodiimide (DCC) (267 mg, 1.296 mmols). The mixture is stirred at room temperature for a while until insolubles have begun to separate out. Then, after addition of p-dimethylaminopyridine (DMAP) (50.8 mg, 0.416 mmol), the reaction mixture is stirred at room temperature overnight. The insolubles are filtered off, the filtrate is 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. After the solvent is distilled off, the residue is chromatographed on a column of silica gel (75 g) and elution is carried out with ethyl acetate, the eluate being collected in 16-g fractions. Fractions 14 through 30 are pooled and the solvent is distilled off to recover 59 mg of crude product. This crude product is dissolved in ethyl acetate, followed by addition of ether, whereby 24.3 mg of maytansinol 3-cyclohexanecarboxylate is obtained as crystals melting at 202°-206° C. (decompn.)

Workup

  1. customto separate out
  2. stirringthe reaction mixture is stirred at room temperature overnight
  3. filtrationThe insolubles are filtered off
  4. washthe filtrate is washed with 0.5 N HCl (ca. 10 ml) and saturated aqueous sodium hydrogen carbonate (ca. 10 ml) in that order
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationAfter the solvent is distilled off
  7. customthe residue is chromatographed on a column of silica gel (75 g) and elution
  8. customthe eluate being collected in 16-g fractions
  9. distillationthe solvent is distilled off
  10. customto recover 59 mg of crude product
  11. dissolutionThis crude product is dissolved in ethyl acetate
  12. additionfollowed by addition of ether

Sources & evidence

ORD record
ord-a62f670448374653b3073c1cb96a83a7
Source dataset
uspto-grants-1981_02
Patent number
US04248870

Reaction notes

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