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

HRID 380951

反応式

HRID 380951 の反応式
[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]

参加物

7

反応物 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、化合物

生成物 1

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

試薬・触媒・溶媒 2

HCID 8003Pentane溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-355dfbb0a3314132a6e076fdf3380959
出典データセット
uspto-grants-2001_10
特許番号
US06303780B1

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