Hydrochloric Acid → (S)-2-[(8-Azaspiro[4.5]decane-8-carbonyl)amino]-4,4-difluoro-5-phenylpentanoic acid

HRID 1913329Notes

Reaction equation

HRID 1913329 reaction equation
[CH2:1]1[C:5]2([CH2:10][CH2:9][N:8]([C:11]([NH:13][C@@H:14]([CH2:19][C:20]([F:29])([F:28])[CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:15]([O:17]C)=[O:16])=[O:12])[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[Li+].[OH-].Cl>C1COCC1.CO.O>[CH2:4]1[C:5]2([CH2:6][CH2:7][N:8]([C:11]([NH:13][C@@H:14]([CH2:19][C:20]([F:29])([F:28])[CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:15]([OH:17])=[O:16])=[O:12])[CH2:9][CH2:10]2)[CH2:1][CH2:2][CH2:3]1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 66661189Methyl (S)-2-[(8-azaspiro[4.5]decane-8-carbonyl)amino]-4,4-difluoro-5-phenylpentanoate

Product 1

HCID 66661164(S)-2-[(8-Azaspiro[4.5]decane-8-carbonyl)amino]-4,4-difluoro-5-phenylpentanoic acid

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Methyl (S)-2-[(8-azaspiro[4.5]decane-8-carbonyl)amino]-4,4-difluoro-5-phenylpentanoate (240 mg, 0.59 mmol) was dissolved in a mixture of 15 ml of THF and 5 ml of methanol. A solution of 42 mg of LiOH (1.76 mmol, 3 eq.) in 5 ml of water was added and the mixture was stirred at RT for 3 h. After the reaction had ended, the reaction mixture was acidified to pH=3 by adding a 2 M HCl solution. The organic solvent was removed under reduced pressure and the remaining aqueous phase was extracted with ethyl acetate. Subsequently, the organic phase was washed another three times with water and once with saturated NaCl solution, dried over MgSO4 and freed from the solvent under reduced pressure. The product was obtained in the form of a yellow solid which was used in the reaction which followed without further purification.

Workup

  1. customThe organic solvent was removed under reduced pressure
  2. extractionthe remaining aqueous phase was extracted with ethyl acetate
  3. washSubsequently, the organic phase was washed another three times with water
  4. dry with materialonce with saturated NaCl solution, dried over MgSO4
  5. customThe product was obtained in the form of a yellow solid which
  6. customwas used in the reaction which
  7. customfollowed without further purification

Sources & evidence

ORD record
ord-7776a04c9119419695acade8134f3f11
Source dataset
uspto-grants-2013_12
Patent number
US08609681B2

Reaction notes

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