5-Fluoroindole-2-carboxylic acid → 4-Benzyloxy-3-hydroxymethylaniline

HRID 32328

반응식

HRID 32328 반응식
F[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7]C(C(O)=O)=C2.FC1C=C2C(=CC=1)NC([C:24](O)=[O:25])=C2C1C=CC=CC=1.CCN(C(C)C)[CH:36]([CH3:38])[CH3:37].C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[CH2:66]1[CH2:70][O:69][CH2:68][CH2:67]1>C(Cl)Cl.C1COCC1.CCOC(C)=O.C(Cl)Cl>[CH2:68]([O:69][C:2]1[CH:10]=[CH:9][C:8]([NH2:7])=[CH:4][C:3]=1[CH2:24][OH:25])[C:67]1[CH:66]=[CH:70][CH:38]=[CH:36][CH:37]=1

참가 물질

9

반응물 5

HCID 18205-Fluoroindole-2-carboxylic acidHCID 8028Tetrahydrofuran2회HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 219043535-Fluoro-3-phenyl-1H-indole-2-carboxylic acid

생성물 1

HCID 219043564-Benzyloxy-3-hydroxymethylaniline

시약·촉매·용매 3

HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매HCID 21919333Tetrahydrofurane dichloromethane용매

실험 절차

A mixture of an amine (see Table 1 below for amines) (0.1 mmol), an acid (5-fluoroindole-2-carboxylic acid or 5-fluoro-3-phenylindole-2-carboxylic acid) (0.1 mmol as 0.1 mL of 1M solution in THF), and DIEA (0.05 mL, 0.3 mmol) in 0.4 mL of CH2Cl2-THF (3:1) was cooled to 0° C. PyBrOP (0.1 mmol) was added. The reaction mixture was shaken using an orbital shaker at 0° C. for 30 minutes then at room temperature for 48 hours (0.1 mL THF and 0.2 mL CH2Cl2 were added after 24 hours). EtOAc was added to the mixture and the organic solution was washed with 1M HCl (2×1 mL), brine (1 mL) NaHCO3 (2×1 mL), and brine (1 mL). The organic layer was passed through a silica gel cartridge containing a top layer of anhydrous MgSO4 and moistened with hexane. The product amide was eluted with hexane (1×1 mL), hexane-EtOAc 2:1 (3×1 mL), hexane-EtOAc 1:1 (2×2 mL), and hexane-EtOAc 1:2 (1×2 mL). The fraction(s) containing pure product was identified by TLC (EtOAc-hexane 1:1 and EtOAc-hexane 1:2 in the case of 5-fluoro-3-phenylindole-2-carboxylic acid amide derivatives). The compounds were characterized by 1H NMR.

후처리

  1. customat 0° C.
  2. customfor 30 minutes
  3. washthe organic solution was washed with 1M HCl (2×1 mL), brine (1 mL) NaHCO3 (2×1 mL), and brine (1 mL)
  4. additioncontaining a top layer of anhydrous MgSO4
  5. washThe product amide was eluted with hexane (1×1 mL), hexane-EtOAc 2:1 (3×1 mL), hexane-EtOAc 1:1 (2×2 mL), and hexane-EtOAc 1:2 (1×2 mL)
  6. additionThe fraction(s) containing pure product

출처 및 근거

ORD 기록
ord-7ae89fc2f3e747d08ebce64e7c2e1931
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07427608B2

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