Lithium Hydroxide → HCID 67288287, compound

HRID 403416Notes

Reaction equation

HRID 403416 reaction equation
[OH:1][C@H:2]1[CH2:36][N:5]2[C:6](=[O:35])[C@@H:7]([NH:26][C:27]([C:29]3[CH:33]=[C:32]([CH3:34])[O:31][N:30]=3)=[O:28])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH:13]=[CH:14][CH:15]3[CH2:20][C@@:16]3([C:21]([O:23]CC)=[O:22])[NH:17][C:18](=[O:19])[C@@H:4]2[CH2:3]1.[Li+].[OH-]>C1COCC1.CO.ClCCl>[OH:1][C@H:2]1[CH2:36][N:5]2[C:6](=[O:35])[C@@H:7]([NH:26][C:27]([C:29]3[CH:33]=[C:32]([CH3:34])[O:31][N:30]=3)=[O:28])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH:13]=[CH:14][CH:15]3[CH2:20][C@@:16]3([C:21]([OH:23])=[O:22])[NH:17][C:18](=[O:19])[C@@H:4]2[CH2:3]1

Participants

6

Reactant 2

HCID 3939Lithium HydroxideHCID 67288735HCID 67288735, compound

Product 1

HCID 67288287HCID 67288287, compoundYield 77%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
10 °C

Procedure

To a solution of (2R,6S,14aR,16aS,Z)-ethyl 2-hydroxy-6-(5-methylisoxazole-3-carboxamido)-5,16-dioxo-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 in THF (62.5 grams, 16% w/w, 10 g starting material) and methanol (33 mL) at 0° C. was added 10% aq. LiOH (14.3 g, 3 equiv) keeping the temperature below 10° C. The solution was stirred at 10° C. for 22 h, then diluted with dichloromethane (150 mL). The reaction mixture was extracted with 1N HCl (100 mL) followed by water (100 mL). The solvent was changed to acetonitrile by distillation. The final acetonitrile level was approximately 70 mL. The slurry in acetonitrile was heated to 50° C. for 4 h, then allowed to cool to ambient temperature for 12 h. The slurry was filtered and the cake was washed with acetonitrile (20 mL) then dried in a vacuum at 50° C. (8.5 g, 86% pure, 77% yield of the title compound).

Workup

  1. customthe temperature below 10° C
  2. extractionThe reaction mixture was extracted with 1N HCl (100 mL)
  3. distillationThe solvent was changed to acetonitrile by distillation
  4. temperatureThe slurry in acetonitrile was heated to 50° C. for 4 h
  5. temperatureto cool to ambient temperature for 12 h
  6. filtrationThe slurry was filtered
  7. washthe cake was washed with acetonitrile (20 mL)

Sources & evidence

ORD record
ord-5b86e9a96e29455aa22952cb82891a38
Source dataset
uspto-grants-2014_06
Patent number
US08748374B2

Reaction notes

Loading…