HCID 68008794, compound → HCID 68009052, compound

HRID 1429081Notes

Reaction equation

HRID 1429081 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]([OH:28])[CH2:27][C@H:21]2[C:20](=[O:29])[NH:19][C@:18]2([C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH2:30][C@H:17]2[CH2:16][C:15]([F:37])([F:36])[CH2:14][CH2:13][CH:12]=[CH:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H][H]>C(OCC)(=O)C.[Pd]>[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C:23](=[O:24])[N:22]2[CH2:25][C@H:26]([OH:28])[CH2:27][C@H:21]2[C:20](=[O:29])[NH:19][C@:18]2([C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH2:30][C@H:17]2[CH2:16][C:15]([F:36])([F:37])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

5

Reactant 2

HCID 68008794HCID 68008794, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 68009052HCID 68009052, compoundYield 95%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent2×

Procedure

A solution of (2R,6S,13aS,14aR,16aS,E)-ethyl 6-(tert-butoxycarbonylamino)-12,12-difluoro-2-hydroxy-5,16-dioxo-1,2,3,5,6,7,10,11,12,13,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo [1,2-a][1,4]diazacyclopentadecine-14a-carboxylate (Example 7h, 1.06 g, 2.002 mmol) in ethyl acetate (50 ml) at 25° C. was added 10% palladium/carbon (0.170 g, 0.160 mmol). The reaction mixture was stirred under a balloon of hydrogen for 2 days. The reaction mixture was filtered through a small plug of silica gel and eluted with ethyl acetate then methanol. The solvent was evaporated under reduced pressure and the resulting solid was purified by flash chromatography on silica gel (40% ethyl acetate/dichloromethane, then ethyl acetate) to provide (2R,6S,13aS,14aR,16aS)-ethyl 6-(tert-butoxycarbonylamino)-12,12-difluoro-2-hydroxy-5,16-dioxooctadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylate (1.01 g, 1.900 mmol, 95% yield) as a white solid. MS (ESI): m/z=532.3 [M+H].

Workup

  1. filtrationThe reaction mixture was filtered through a small plug of silica gel
  2. washeluted with ethyl acetate
  3. customThe solvent was evaporated under reduced pressure
  4. customthe resulting solid was purified by flash chromatography on silica gel (40% ethyl acetate/dichloromethane

Sources & evidence

ORD record
ord-8a666c558d1c4d3e9a099737499415b9
Source dataset
uspto-grants-2015_01
Patent number
US08937041B2

Reaction notes

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