6-Azaspiro[2.5]octane trifluoroacetate → methyl (S)-2-[(6-azaspiro[2.5]octane-6-carbonyl)amino]-4,4-difluoro-5-phenylpentanoate

HRID 1913342Notes

Reaction equation

HRID 1913342 reaction equation
[F:1][C:2]([F:19])([CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:3][C@H:4]([N:9]=[C:10]=[O:11])[C:5]([O:7][CH3:8])=[O:6].FC(F)(F)C(O)=O.[CH2:27]1[C:29]2([CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)[CH2:28]1>>[CH2:28]1[C:29]2([CH2:34][CH2:33][N:32]([C:10]([NH:9][C@@H:4]([CH2:3][C:2]([F:19])([F:1])[CH2:12][C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:5]([O:7][CH3:8])=[O:6])=[O:11])[CH2:31][CH2:30]2)[CH2:27]1

Participants

3

Reactant 2

HCID 666613976-Azaspiro[2.5]octane trifluoroacetateHCID 86635603Methyl (S)-4,4-difluoro-2-isocyanato-5-phenylpentanoate

Product 1

HCID 57946183methyl (S)-2-[(6-azaspiro[2.5]octane-6-carbonyl)amino]-4,4-difluoro-5-phenylpentanoate

Procedure

Methyl (S)-2-[(6-azaspiro[2.5]octane-6-carbonyl)amino]-4,4-difluoro-5-phenylpentanoate was prepared analogously to example 61, starting from 904 mg of methyl (S)-4,4-difluoro-2-isocyanato-5-phenylpentanoate (3.36 mmol) and 907 mg of 6-azaspiro[2.5]octane trifluoroacetate (1.2 eq.). Chromatographic separation by preparative HPLC (gradient: acetonitrile/water and addition of 0.05% TFA) gave methyl (S)-2-[(6-azaspiro[2.5]octane-6-carbonyl)amino]-4,4-difluoro-5-phenylpentanoate as a yellow oil. Yield: 234 mg (18% of theory)

Workup

  1. customMethyl (S)-2-[(6-azaspiro[2.5]octane-6-carbonyl)amino]-4,4-difluoro-5-phenylpentanoate was prepared analogously to example 61
  2. customChromatographic separation
  3. additionby preparative HPLC (gradient: acetonitrile/water and addition of 0.05% TFA)

Sources & evidence

ORD record
ord-41dacaca47b24829880aaa2f63a14d8f
Source dataset
uspto-grants-2013_12
Patent number
US08609681B2

Reaction notes

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