m-Chloroperbenzoic acid → Cryptophycin-292

HRID 352290Notes

Reaction equation

HRID 352290 reaction equation
[CH3:1][CH:2]1[C:20](=[O:21])[O:19][CH:18]([CH2:22][CH:23]([CH3:25])[CH3:24])[C:16](=[O:17])[O:15][CH:14]([CH:26]([CH:28]2[O:30][CH:29]2[C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH3:27])[CH2:13][CH:12]=[CH:11][C:9](=[O:10])[NH:8][CH:7]([CH2:37][C:38]2[CH:43]=[CH:42][C:41]([O:44][CH3:45])=[C:40]([Cl:46])[CH:39]=2)[C:5](=[O:6])[NH:4][CH2:3]1.Cl[C:48]1C=CC=C(C(OO)=O)C=1>C(Cl)(Cl)Cl>[CH3:1][C@H:2]1[C:20](=[O:21])[O:19][C@@H:18]([CH2:22][C:23]([CH3:48])([CH3:24])[CH3:25])[C:16](=[O:17])[O:15][C@H:14]([C@@H:26]([C@H:28]2[O:30][C@@H:29]2[C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH3:27])[CH2:13][CH:12]=[CH:11][C:9](=[O:10])[NH:8][C@H:7]([CH2:37][C:38]2[CH:43]=[CH:42][C:41]([O:44][CH3:45])=[C:40]([Cl:46])[CH:39]=2)[C:5](=[O:6])[NH:4][CH2:3]1

Participants

4

Reactant 2

HCID 70297m-Chloroperbenzoic acidHCID 5468287(13E)-10-[(3-chloro-4-methoxyphenyl)methyl]-6-methyl-3-(2-methylpropyl)-16-[1-(3-phenyloxiran-2-yl)ethyl]-1,4-dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetrone

Product 1

HCID 101078491Cryptophycin-292Yield 103.6%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

A solution of Cryptophycin 289 (13.2 g, 20.2 mmol) in chloroform (43 mL) is stirred and treated with m-chloroperbenzoic acid (m-CPBA) (95% pure, 5.19 g, 30.1 mmol). After stirring overnight at room temperature, the solution is diluted with chloroform until clear, washed with sodium bicarbonate (saturated aqueous, 100 mL), sodium sulfite (saturated aqueous, 100 mL), sodium chloride (saturated aqueous, 100 mL), dried (magnesium sulfate), filtered, and the filtrate evaporated (40° C., 20 mm Hg) to provide 14 g of the Cryptophycin-292 as a mixture of epoxide isomers, as a white foam. The foam is dissolved in chloroform, cooled to −63° C., and treated with chlorotrimethylsilane (23.5 mL, 185 mmol) via syringe. The mixture is stirred at −63° C. for 5 hours, then allowed to stand in the freezer at −20° C. overnight. The mixture is again cooled to −63° C. and treated with sodium bicarbonate (saturated aqueous, 60 mL) with vigorous stirring. The cold bath is removed and the mixture allowed to warm to room temperature over a 1 hour period. The layers are separated and the aqueous layer extracted with chloroform. The organic layers are washed with sodium bicarbonate (saturated aqueous, 60 mL), sodium chloride (saturated aqueous, 100 mL), dried (magnesium sulfate), filtered, and the filtrate evaporated to 14 g of a white residue. The residue is chromatographed on silica gel (70×160 mm of silica gel, packed and eluted in 2:1:1 tBuOMe/CH2Cl2/hexanes) to provide 4.51 g of Cryptophycin 296 as a colorless foam (32%)

Workup

  1. washwashed with sodium bicarbonate (saturated aqueous, 100 mL), sodium sulfite (saturated aqueous, 100 mL), sodium chloride (saturated aqueous, 100 mL)
  2. dry with materialdried (magnesium sulfate)
  3. filtrationfiltered
  4. customthe filtrate evaporated (40° C., 20 mm Hg)

Sources & evidence

ORD record
ord-095e624933dc4996968068162057c3c8
Source dataset
uspto-grants-2004_06
Patent number
US06747021B2

Reaction notes

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