Lithium Hydroxide → HCID 67288287, compound

HRID 403426Notes

Reaction equation

HRID 403426 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 (10 g) in THF (52 g) and methanol (33 mL) at 0° C. was added 10% aq. LiOH (14.3 g). 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 and the product crystallized. The final acetonitrile level was approximately 70 mL. The slurry 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 under vacuum at 50° C. (8.5 g, 86% pure, 77% yield).

Workup

  1. extractionThe reaction mixture was extracted with 1N HCl (100 mL)
  2. distillationThe solvent was changed to acetonitrile by distillation
  3. customthe product crystallized
  4. temperatureThe slurry 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)
  8. customthen dried under vacuum at 50° C. (8.5 g, 86% pure, 77% yield)

Sources & evidence

ORD record
ord-06ba7de2377646c8bb297171638f809b
Source dataset
uspto-grants-2014_06
Patent number
US08748374B2

Reaction notes

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