1,1'-Carbonyldiimidazole → 4-Amino-5-chloro-2-methoxybenzoic acid 1-azabicyclo[3.3.1]non-5-ylmethyl ester

HRID 5385

반응식

HRID 5385 반응식
[NH2:1][C:2]1[C:10]([Cl:11])=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([O:12][CH3:13])[CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[N:26]12[CH2:34][C:30]([CH2:35]O)([CH2:31][CH2:32][CH2:33]1)[CH2:29][CH2:28][CH2:27]2.C([Li])CCC.CCCCCC>O1CCCC1>[N:26]12[CH2:34][C:30]([CH2:35][O:7][C:6](=[O:8])[C:5]3[CH:9]=[C:10]([Cl:11])[C:2]([NH2:1])=[CH:3][C:4]=3[O:12][CH3:13])([CH2:31][CH2:32][CH2:33]1)[CH2:29][CH2:28][CH2:27]2

참가 물질

6

반응물 4

HCID 682631,1'-CarbonyldiimidazoleHCID 816264-Amino-5-chloro-2-methoxybenzoic acidHCID 19795980{1-Azabicyclo[3.3.1]nonan-5-yl}methanolHCID 178418244HCID 178418244, 화합물

생성물 1

HCID 539303044-Amino-5-chloro-2-methoxybenzoic acid 1-azabicyclo[3.3.1]non-5-ylmethyl ester수율 57.3%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

A solution of 4-amino-5-chloro-2-methoxybenzoic acid (2.02 g, 10 mmol) in anhydrous tetrahydrofuran (10 mL) under nitrogen was treated with 1,1'-carbonyldiimidazole (1.70 g, 10.5 mmol), stirred for one hour, then degassed with a stream of nitrogen over 10 minutes. Meanwhile, a cooled (-10° C.) solution of 1-azabicyclo[3.3.1]nonane-5-methanol (1.71 g, 11 mmol) in anhydrous tetrahydrofuran (10 mL) under nitrogen was treated (via syringe) with 2.5N n-butyllithium/hexane (10.7 mmol), stirred for 30 minutes, concentrated in vacuo, and taken up in anhydrous tetrahydrofuran (10 mL) under nitrogen. The above prepared suspension was transferred into this solution, and the mixture was stirred overnight (18 hours) and concentrated in vacuo. The residue was partitioned between methylene chloride (100 mL) containing a little 2-propanol and saturated aqueous sodium carbonate (50 mL), and the organic layer was separated. The aqueous solution was extracted with methylene chloride (2×50 mL), and the combined organic solution was dried (Na2SO4), concentrated in vacuo and recrystallized from acetonitrile (2 crops) to afford 1.94 g (57%) of pale yellow solid; mp 152.5°-154.5° C.

후처리

  1. customdegassed with a stream of nitrogen over 10 minutes
  2. stirringstirred for 30 minutes
  3. concentrationconcentrated in vacuo
  4. customThe above prepared suspension
  5. stirringthe mixture was stirred overnight (18 hours)
  6. concentrationconcentrated in vacuo
  7. customThe residue was partitioned between methylene chloride (100 mL)
  8. additioncontaining a little 2-propanol and saturated aqueous sodium carbonate (50 mL)
  9. customthe organic layer was separated
  10. extractionThe aqueous solution was extracted with methylene chloride (2×50 mL)
  11. dry with materialthe combined organic solution was dried (Na2SO4)
  12. concentrationconcentrated in vacuo
  13. customrecrystallized from acetonitrile (2 crops)

출처 및 근거

ORD 기록
ord-9f608317b9754efda2c9e04eca249eb4
출처 데이터셋
uspto-grants-1993_09
특허 번호
US05244907

연결된 노트

불러오는 중…