Hydrochloric Acid → HCID 5358230, compound

HRID 127568Notes

Reaction equation

HRID 127568 reaction equation
CCC([O:5][C@@H:6]1[C@:28]2([CH3:30])[O:29][C@H:27]2[C@H:26]([CH3:31])[C@H:25]2[O:32][C:33]([NH:35][C@:23]([OH:36])([CH2:24]2)[C@H:22]([O:37][CH3:38])[CH:21]=[CH:20][CH:19]=[C:18]([CH3:39])[CH2:17][C:15]2=[CH:16][C:11](=[C:12]([Cl:42])[C:13]([O:40][CH3:41])=[CH:14]2)[N:10]([CH3:43])[C:8](=[O:9])[CH2:7]1)=[O:34])=O.[H-].[Al+3].[Li+].[H-].[H-].[H-].Cl>O1CCCC1>[CH3:31][CH:26]1[CH:27]2[O:29][C:28]2([CH3:30])[CH:6]([OH:5])[CH2:7][C:8](=[O:9])[N:10]([CH3:43])[C:11]2=[C:12]([Cl:42])[C:13]([O:40][CH3:41])=[CH:14][C:15](=[CH:16]2)[CH2:17][C:18]([CH3:39])=[CH:19][CH:20]=[CH:21][CH:22]([O:37][CH3:38])[C:23]2([OH:36])[NH:35][C:33]([O:32][CH:25]1[CH2:24]2)=[O:34]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 6443033Maytansine, 2-de(acetylmethylamino)-HCID 21226445Aluminium lithium hydride2×

Product 1

HCID 5358230HCID 5358230, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-50 °C

Procedure

In 800 ml of dry tetrahydrofuran (THF) is dissolved 15.0 g of Ansamitocin antibiotic mixture (12% of ansamitocin P-2, 71% of P-3 and 17% of P-4) and under dry nitrogen gas streams, the solution is cooled to -50° C. in a dry ice-acetone bath. Then, 13.0 g of lithium aluminum hydride (LAH) is added in a single dose and the mixture is stirred at -50° C. to -22° C. for 2 hours. Then, at -28° C., a further 3 g of LAH is added and the reaction mixture is stirred at -28° C. to -22° C. for 80 minutes. Thereafter, at -50° C., 750 ml of 2 N HCl is added dropwise with caution and the reaction mixture is extracted three times with 2.6 l, 1.6 l and 0.8 l portions of ethyl acetate. The extracts are pooled, washed with a saturated aqueous solution of sodium chloride (100 ml×2) and dried (MgSO4, 250 g). The solvent is distilled off under reduced pressure and the residue (13.6 g) is chromatographed on a column of silica gel (1.2 kg), elution being carried out with ethyl acetate-water (98.5:1.5, V/V). The eluate is collected in 400-gram fractions. Fractions 35 through 52 are pooled, the solvent distilled off and the residue dried in vacuo to obtain 7.25 g of maytansinol. Then, fractions 53 through 68 are similarly treated to obtain 1.55 g of a substantially equimolar mixture of maytansinol and dechloromaytansinol. Similarly, fractions 69 through 86 yield 0.78 g of dechloromaytansinol.

Workup

  1. stirringthe reaction mixture is stirred at -28° C. to -22° C. for 80 minutes
  2. extractionthe reaction mixture is extracted three times with 2.6 l, 1.6 l and 0.8 l portions of ethyl acetate
  3. washwashed with a saturated aqueous solution of sodium chloride (100 ml×2)
  4. dry with materialdried (MgSO4, 250 g)
  5. distillationThe solvent is distilled off under reduced pressure
  6. customthe residue (13.6 g) is chromatographed on a column of silica gel (1.2 kg), elution
  7. customThe eluate is collected in 400-gram fractions
  8. distillationthe solvent distilled off
  9. customthe residue dried in vacuo

Sources & evidence

ORD record
ord-32e3b3421bb74d3eb5353f54535252cb
Source dataset
uspto-grants-1981_03
Patent number
US04256746

Reaction notes

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