Lithium Hydroxide → HCID 11488860, compound

HRID 1744884Notes

Reaction equation

HRID 1744884 reaction equation
C[O:2][C:3](=[O:35])[CH2:4][C@@H:5]1[C:17]2[N:16]([C@H:18]([C:20]3[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=3)[CH3:19])[C:15]3[C:10](=[CH:11][C:12]([F:34])=[CH:13][C:14]=3[S:30]([CH3:33])(=[O:32])=[O:31])[C:9]=2[CH2:8][CH2:7][CH2:6]1.C1COCC1.CO.[Li+].[OH-]>CC(O)=O>[F:34][C:12]1[CH:11]=[C:10]2[C:15](=[C:14]([S:30]([CH3:33])(=[O:31])=[O:32])[CH:13]=1)[N:16]([C@H:18]([C:20]1[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:27])[F:28])=[CH:22][CH:21]=1)[CH3:19])[C:17]1[C@@H:5]([CH2:4][C:3]([OH:35])=[O:2])[CH2:6][CH2:7][CH2:8][C:9]2=1

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 21899815MeOH tetrahydrofuranHCID 86615645HCID 86615645, compound2×

Product 1

HCID 11488860HCID 11488860, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution of the above ester (1 eq) in a 3.5/1 mixture of THF/MeOH (0.25M) at 0° C. was slowly added aqueous LiOH 1N (1 eq) and the mixture was stirred at 0° C. for 16 h or until almost complete hydrolysis of the ester; under these conditions, the other minor diastereomer has a much slower rate of hydrolysis. AcOH was added and the solvent was removed in vacuo. The residue was taken up in EtOAc/H2O and the organic layer was washed with brine, dried over Na2SO4 filtered and concentrated. To remove the unreacted methyl ester, the residue was filtered through a pad of silica gel eluting first with 10% EtOAc/toluene and then with 60% EtOAc/toluene containing 1% of AcOH. The residue was swished in 30% EtOAc/hexane and dried under high vacuum at 50° C. for 16 hr to give the desired title compound as a white solid with de and ee >95% (checked by chiral HPLC). MS (−APCI) m/z 496.0 (M−H)−. [α]D=−181° in MeOH.

Workup

  1. customa much slower rate of hydrolysis
  2. customthe solvent was removed in vacuo
  3. washthe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customTo remove the unreacted methyl ester
  8. filtrationthe residue was filtered through a pad of silica gel eluting first with 10% EtOAc/toluene
  9. customdried under high vacuum at 50° C. for 16 hr

Sources & evidence

ORD record
ord-017dba42c67c4b6981d5254a58bd25bd
Source dataset
uspto-grants-2006_03
Patent number
US07019022B2

Reaction notes

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