Hydrogen Peroxide → HCID 68008462, compound

HRID 1429099Notes

Reaction equation

HRID 1429099 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C:23](=[O:24])[N:22]2[CH2:25][C@H:26]([O:28][C:29]3[N:30]=[C:31]4[C:36](=[C:37]5[C:42]=3[CH:41]=[CH:40][CH:39]=[CH:38]5)[CH:35]=[CH:34][CH:33]=[CH:32]4)[CH2:27][C@H:21]2[C:20](=[O:43])[NH:19][C@:18]2([C:45]([O:47][CH2:48][CH3:49])=[O:46])[CH2:44][C@H:17]2[CH:16]=[CH:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[O:50]1CCCC1.B.[OH-].[Na+].OO>O1CCCC1.C(OCC)(=O)C.O>[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C:23](=[O:24])[N:22]2[CH2:25][C@H:26]([O:28][C:29]3[N:30]=[C:31]4[C:36](=[C:37]5[C:42]=3[CH:41]=[CH:40][CH:39]=[CH:38]5)[CH:35]=[CH:34][CH:33]=[CH:32]4)[CH2:27][C@H:21]2[C:20](=[O:43])[NH:19][C@:18]2([C:45]([O:47][CH2:48][CH3:49])=[O:46])[CH2:44][C@H:17]2[CH2:16][CH:15]([OH:50])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 2723981Borane;tetrahydrofuranHCID 68499992HCID 68499992, compound

Product 1

HCID 68008462HCID 68008462, compoundYield 32.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (2R,6S,13aS,14aR,16aS,Z)-ethyl 6-(tert-butoxycarbonylamino)-5,16-dioxo-2-(phenanthridin-6-yloxy)-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo [1,2-a][1,4]diazacyclopentadecine-14a-carboxylate (Example 18a, 3.2 g, 4.77 mmol) in tetrahydrofuran (41.5 ml) at rt with a water bath was added dropwise borane tetrahydrofuran complex (1 M in tetrahydrofuran, 14.3 ml, 14.3 mmol) and stirred at room temperature for 1 h. The mixture was cooled to 0° C. and sodium hydroxide (11.5 ml, 28.6 mmol) was added dropwise followed by hydrogen peroxide (4.0 ml, 43 mmol), and the reaction mixture stirred for 1.5 h at 0° C. The mixture was diluted with ethyl acetate and water, and the organic layer was washed with saturated aqueous sodium chloride solution. The resulting solid was purified via flash chromatography on silica gel (5% methanol in dichloromethane) to provide the title compound (2R,6S,13aS,14aR,16aS)-ethyl 6-(tert-butoxycarbonylamino)-12-hydroxy-5,16-dioxo-2-(phenanthridin-6-yloxy)octadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylate (1.06 g, 1.539 mmol, 32.3% yield). The α-hydroxy analog (2R,6S,13R,13aR,14aR,16aS)-ethyl 6-(tert-butoxycarbonylamino)-13-hydroxy-5,16-dioxo-2-(phenanthridin-6-yloxy)octadecahydrocyclopropa[e]pyrrolo [1,2-a][1,4]diazacyclopentadecine-14a-carboxylate (0.7 g, 21% yield) was also isolated.

Workup

  1. temperatureThe mixture was cooled to 0° C.
  2. stirringthe reaction mixture stirred for 1.5 h at 0° C
  3. washthe organic layer was washed with saturated aqueous sodium chloride solution
  4. customThe resulting solid was purified via flash chromatography on silica gel (5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-99600cb2db3d4dafba06c7aa2eedc11b
Source dataset
uspto-grants-2015_01
Patent number
US08937041B2

Reaction notes

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