Potassium Hydroxide → HCID 68009015, compound

HRID 1429071Notes

Reaction equation

HRID 1429071 reaction equation
C([O:9][C@@H:10]1[CH2:45][N:13]2[C:14](=[O:44])[C@@H:15]([NH:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21]([F:35])([F:34])[CH2:22][C@@H:23]3[CH2:28][C@@:24]3([C:29]([O:31][CH2:32][CH3:33])=[O:30])[NH:25][C:26](=[O:27])[C@@H:12]2[CH2:11]1)(=O)C1C=CC=CC=1.[OH-].[K+]>C(O)C>[C:40]([O:39][C:37]([NH:36][C@@H:15]1[C:14](=[O:44])[N:13]2[CH2:45][C@@H:10]([OH:9])[CH2:11][C@H:12]2[C:26](=[O:27])[NH:25][C@:24]2([C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:28][C@H:23]2[CH2:22][C:21]([F:34])([F:35])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1)=[O:38])([CH3:42])([CH3:41])[CH3:43]

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 68008200HCID 68008200, compound

Product 1

HCID 68009015HCID 68009015, compoundYield 115.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (2S,6S,13aS,14aR,16aS)-ethyl 2-(benzoyloxy)-6-(tert-butoxycarbonylamino)-12,12-difluoro-5,16-dioxooctadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylate (Example 1d, 94.75 mg, 0.149 mmol) in ethanol (0.414 ml) at 0° C. was added dropwise a solution of KOH (0.25 ml, 0.250 mmol, 1 N in ethanol). The solution was stirred at 0° C. for 50 min and LC/MS showed completion. The reaction mixture was quenched by dropwise addition of HCl (1 N in dioxane/ethyl acetate, 0.25 ml) at 0° C. Another portion of (2S,6S,13aS,14aR,16aS)-ethyl 2-(benzoyloxy)-6-(tert-butoxycarbonylamino)-12,12-difluoro-5,16-dioxooctadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylate (14.36 mg) was reacted under similar condition. Materials from these two reactions were combined and purified by reverse phase HPLC (acetonitrile/water (0.1% TFA)=30/70 to 100/0, 15 min) to provide the title compound (2S,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 (91.3 mg) MS (ESI): m/z=532.2 [M+H].

Workup

  1. customThe reaction mixture was quenched by dropwise addition of HCl (1 N in dioxane/ethyl acetate, 0.25 ml) at 0° C
  2. customAnother portion of (2S,6S,13aS,14aR,16aS)-ethyl 2-(benzoyloxy)-6-(tert-butoxycarbonylamino)-12,12-difluoro-5,16-dioxooctadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylate (14.36 mg) was reacted under similar condition
  3. custompurified by reverse phase HPLC (acetonitrile/water (0.1% TFA)=30/70 to 100/0, 15 min)

Sources & evidence

ORD record
ord-ca194864c9f44cd185c60695a002cfb7
Source dataset
uspto-grants-2015_01
Patent number
US08937041B2

Reaction notes

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