Ethanol → HCID 68008421, compound

HRID 1429100Notes

Reaction equation

HRID 1429100 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]CC)=[O:46])[CH2:44][C@H:17]2[CH2:16][C:15]([F:51])([F:50])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(O)C.O.[OH-].[Li+]>O1CCCC1.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]([OH:47])=[O:46])[CH2:44][C@H:17]2[CH2:16][C:15]([F:50])([F:51])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 702EthanolHCID 168937Lithium hydroxide, monohydrateHCID 68008696HCID 68008696, compound

Product 1

HCID 68008421HCID 68008421, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (2R,6S,13aS,14aR,16aS)-ethyl 6-(tert-butoxycarbonylamino)-12,12-difluoro-5,16-dioxo-2-(phenanthridin-6-yloxy)octadecahydrocyclopropa[e]pyrrolo [1,2-a][1,4]diazacyclo pentadecine-14a-carboxylate (Example 19c, 320 mg, 0.451 mmol) in tetrahydrofuran (1505 μl), water (752 μl), and ethanol (752 μl) was added lithium hydroxide monohydrate (123 mg, 2.93 mmol) at room temperature The mixture was stirred at room temperature for 16 h and then heated at 37° C. for 6h. The mixture was cooled to room temperature and then eluted through a pad of silica gel with 10% methanol/dichloromethane,and evaporated under reduced pressure. The crude materal was purified by flash chromatography on silica gel (10% methanol/dichloromethane) to provide the title compound (2R,6S,13aS,14aR,16aS)-6-(tert-butoxycarbonylamino)-12,12-difluoro-5,16-dioxo-2-(phenanthridin-6-yloxy)octadeca hydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylic acid (215 mg, 70.0% yield) as a white solid.

Workup

  1. temperatureheated at 37° C. for 6h
  2. temperatureThe mixture was cooled to room temperature
  3. washeluted through a pad of silica gel with 10% methanol/dichloromethane,and
  4. customevaporated under reduced pressure
  5. customThe crude materal was purified by flash chromatography on silica gel (10% methanol/dichloromethane)

Sources & evidence

ORD record
ord-90816478f33b4856b7fab6c43841c9a7
Source dataset
uspto-grants-2015_01
Patent number
US08937041B2

Reaction notes

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