Hydrochloric Acid → (S)-2-[(6-azaspiro[2.5]octane-6-carbonyl)amino]-4,4-difluoropentanoic acid

HRID 1913337Notes

Reaction equation

[CH2:1]1[C:3]2([CH2:8][CH2:7][N:6]([C:9]([NH:11][C@@H:12]([CH2:17][C:18]([F:21])([F:20])[CH3:19])[C:13]([O:15]C)=[O:14])=[O:10])[CH2:5][CH2:4]2)[CH2:2]1.[Li+].[OH-].Cl>C1COCC1.CO>[CH2:2]1[C:3]2([CH2:8][CH2:7][N:6]([C:9]([NH:11][C@@H:12]([CH2:17][C:18]([F:21])([F:20])[CH3:19])[C:13]([OH:15])=[O:14])=[O:10])[CH2:5][CH2:4]2)[CH2:1]1

Participants

Conditions

Temperature: 45 °C

Procedure

365.0 mg of methyl (S)-2-[(6-azaspiro[2.5]octane-6-carbonyl)amino]-4,4-difluoropentanoate (1.2 mmol) were dissolved in a mixture of 10.8 ml of THF and 3.6 ml of methanol. 3.6 ml of an aqueous 1 M LiOH solution (3 eq.) were added to this solution. The mixture was stirred at 45° C. (bath temperature) for one hour and then 3.6 ml of 1 M HCl solution were added. The mixture was concentrated under reduced pressure and codistilled with DMF twice more. The (S)-2-[(6-azaspiro[2.5]octane-6-carbonyl)amino]-4,4-difluoropentanoic acid thus obtained was clean enough for the next reaction. Yield: 400 mg (quant.)

Workup

concentrationThe mixture was concentrated under reduced pressure

Sources & evidence

ORD record: ord-a914a3f3ddaa4cb991c95a79550ddca0
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08609681B2

Reaction notes

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