Citric Acid → 2-(5-(t-Butoxycarbonylamino)-2-chloropyrid-4-yl)-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-ol

HRID 380951

반응식

HRID 380951 반응식
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[CH:11][C:12]([Cl:15])=[N:13][CH:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li]C(C)(C)C.[CH:21]1([C:24]#[C:25][C:26](=[O:31])[C:27]([F:30])([F:29])[F:28])[CH2:23][CH2:22]1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.CCCCC>[C:1]([O:5][C:6]([NH:8][C:9]1[C:10]([C:26]([OH:31])([C:25]#[C:24][CH:21]2[CH2:22][CH2:23]2)[C:27]([F:28])([F:29])[F:30])=[CH:11][C:12]([Cl:15])=[N:13][CH:14]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

참가 물질

7

반응물 4

HCID 311Citric AcidHCID 7330593(6-Chloro-pyridin-3-yl)-carbamic acid tert-butyl esterHCID 106308184-Cyclopropyl-1,1,1-trifluoro-3-butyn-2-oneHCID 178418306HCID 178418306, 화합물

생성물 1

HCID 183865642-(5-(t-Butoxycarbonylamino)-2-chloropyrid-4-yl)-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-ol

시약·촉매·용매 2

HCID 8003Pentane용매HCID 8028Tetrahydrofuran용매

실험 절차

To a stirred, cooled (−50° C.) solution of 643 mg(2.8 mmol) of 5-(t-butoxycarbonylamino)-2-chloropyridine in 8 mL of anhydrous THF was added 4.7 mL(7.9 mmol) of t-BuLi in pentane over 3 min. The solution was stirred an additional 35 min. at −50° C. after which time 1 mL(large excess) of 4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-one. The solution was stirred an additional 20 min., warming to ambient temperature. The reaction was poured into 10% aq. citric acid, and the mixture was extracted with 1:1 ether-ethyl acetate. The organic extract was washed with saturated aq. NaHCO3, then brine, dried (MgSO4), and concentrated under reduced pressure. Chromatography on silica gel(gradient elution with 6:1 then 3:1 hexanes-ethyl acetate) afforded, after removal of solvent, 620 mg(56%) of 2-(5-(t-butoxycarbonylamino)-2-chloropyrid-4-yl)-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-ol as an amorphous solid. Mass spec.(NH3—CI): 391((M+H)+, 100%); 291((M+H-t-Boc)+, 49%). 1H NMR(300 MHz, CDCl3) δ 9.08(br. s, 1H); 8.29(br. s, 1H); 7.59(s, 1H); 1.50(s, 9H); 1.37-1.43(m, 1H); 0.81-0.97(m, 4H).

후처리

  1. extractionthe mixture was extracted with 1:1 ether-ethyl acetate
  2. extractionThe organic extract
  3. washwas washed with saturated aq. NaHCO3
  4. dry with materialbrine, dried (MgSO4)
  5. concentrationconcentrated under reduced pressure
  6. washChromatography on silica gel(gradient elution with 6:1
  7. custom3:1 hexanes-ethyl acetate) afforded
  8. customafter removal of solvent, 620 mg(56%) of 2-(5-(t-butoxycarbonylamino)-2-chloropyrid-4-yl)-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-ol as an amorphous solid

출처 및 근거

ORD 기록
ord-355dfbb0a3314132a6e076fdf3380959
출처 데이터셋
uspto-grants-2001_10
특허 번호
US06303780B1

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