Lithium Hydroxide → 2-[(4'-Methoxy[1,1'-biphenyl]-4-yl)sulfonyl]amino-3-phenylmethoxy-4-hydroxy-5-[(2-thiazolyl)thio]-pentanoic Acid

HRID 413408Notes

Reaction equation

HRID 413408 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([S:15]([NH:18][CH:19]3[CH:23]([O:24][CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[CH:22]([CH2:32][S:33][C:34]4[S:35][CH:36]=[CH:37][N:38]=4)[O:21][C:20]3=[O:39])(=[O:17])=[O:16])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.[OH-:40].[Li+]>C1COCC1.O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([S:15]([NH:18][CH:19]([CH:23]([O:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH:22]([OH:40])[CH2:32][S:33][C:34]3[S:35][CH:36]=[CH:37][N:38]=3)[C:20]([OH:21])=[O:39])(=[O:16])=[O:17])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 235082843-[(4'-Methoxy[1,1'-biphenyl]-4-yl)sulfonyl]amino-2-oxo-4-phenylmethoxy-5-[[(2-thiazolyl)thio]methyl]-tetrahydrofuran

Product 1

HCID 235082542-[(4'-Methoxy[1,1'-biphenyl]-4-yl)sulfonyl]amino-3-phenylmethoxy-4-hydroxy-5-[(2-thiazolyl)thio]-pentanoic Acid

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

The 3-[(4′-Methoxy[1,1′-biphenyl]-4-yl)sulfonyl]amino-2-oxo-4-phenylmethoxy-5-[[(2-thiazolyl)thio]methyl]-tetrahydrofuran 63f, 154 mg, 0.258 mmol) is dissolved in THF/water (2 mL/2 mL) and lithium hydroxide (108 mg, 2.58 mmol) is added and the reaction is stirred for two hours at room temperature. The reaction is concentrated to remove the solvent, diluted with water and extracted (2 times) with ether. The aqueous layer is neutralized with 1N HCl to pH6 and extracted with ethyl acetate (3 times). The combined organic layer is washed with brine, dried over magnesium sulfate, and the solvent removed in vacuo. The crude material is adsorbed onto silica gel and purified over a short silica column eluting with hexane/ethyl acetate (1/1) followed with ethyl acetate and ethyl acetate/methanol (8/2). Product fractions are combined and dried to give the desired product as a white solid.

Workup

  1. concentrationThe reaction is concentrated
  2. customto remove the solvent
  3. additiondiluted with water
  4. extractionextracted (2 times) with ether
  5. extractionextracted with ethyl acetate (3 times)
  6. washThe combined organic layer is washed with brine
  7. dry with materialdried over magnesium sulfate
  8. customthe solvent removed in vacuo
  9. custompurified over a short silica column
  10. washeluting with hexane/ethyl acetate (1/1)
  11. customdried

Sources & evidence

ORD record
ord-3b4db11f39014710806b20be3f9c2306
Source dataset
uspto-grants-2003_05
Patent number
US06566381B1

Reaction notes

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