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

HRID 1913336노트

반응식

HRID 1913336 반응식
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

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 63651,1-Dichloroethane용매2회

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-75891ce8591e4fbaa98b10c34b26b619
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08609681B2

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