Diisopropylethylamine → Methyl (S)-2-[(6-azaspiro[2.5]octane-6-carbonyl)amino]-4,4-difluoropentanoate

HRID 1664728Notes

Reaction equation

HRID 1664728 reaction equation
FC(F)(F)C(O)=O.[CH2:8]1[C:10]2([CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[CH2:9]1.CCN(C(C)C)C(C)C.[F:25][C:26]([F:37])([CH3:36])[CH2:27][C@H:28]([N:33]=[C:34]=[O:35])[C:29]([O:31][CH3:32])=[O:30]>ClC(Cl)C.ClCCl>[CH2:9]1[C:10]2([CH2:15][CH2:14][N:13]([C:34]([NH:33][C@@H:28]([CH2:27][C:26]([F:25])([F:37])[CH3:36])[C:29]([O:31][CH3:32])=[O:30])=[O:35])[CH2:12][CH2:11]2)[CH2:8]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 57946243Methyl (S)-4,4-difluoro-2-isocyanatopentanoateHCID 666613976-Azaspiro[2.5]octane trifluoroacetate

Product 1

HCID 57946179Methyl (S)-2-[(6-azaspiro[2.5]octane-6-carbonyl)amino]-4,4-difluoropentanoate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent2×

Procedure

A solution of 0.75 g of 6-azaspiro[2.5]octane trifluoroacetate (3.30 mmol, 1 eq.) and 0.75 ml of DIPEA (1.3 eq.) in 6 ml of dichloroethane was added under argon to a solution of 0.65 g of methyl (S)-4,4-difluoro-2-isocyanatopentanoate (3.36 mmol) in 4 ml of dichloroethane. The reaction mixture was stirred at RT overnight. The mixture was diluted with 10 ml of dichloromethane and washed with saturated NaHCO3 solution. The organic phase was dried over MgSO4 and then concentrated under reduced pressure. The residue thus obtained was purified by preparative HPLC (gradient: acetonitrile/water and addition of 0.05% TFA. The product-containing fractions were combined and freeze-dried.

Workup

  1. washwashed with saturated NaHCO3 solution
  2. dry with materialThe organic phase was dried over MgSO4
  3. concentrationconcentrated under reduced pressure
  4. customThe residue thus obtained
  5. customwas purified by preparative HPLC (gradient
  6. additionacetonitrile/water and addition of 0.05% TFA
  7. customfreeze-dried

Sources & evidence

ORD record
ord-060e81a68b014fbd9eeb2227556ecdf1
Source dataset
uspto-grants-2011_10
Patent number
US08039480B2

Reaction notes

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