Formaldehyde → 4-Pyridineacetic acid, 2-bromo-α,α-bis(hydroxymethyl)-, ethyl ester

HRID 474070노트

반응식

HRID 474070 반응식
[CH2:1]([O:3][C:4](=[O:13])[CH2:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8]([Br:12])[CH:7]=1)[CH3:2].[CH2:14]=[O:15].N12CCCN=C1CCCCC2.[C@@]12(CS(O)(=O)=O)C(C)(C)C(CC1)C[C:28]2=[O:29]>C(Cl)Cl>[CH2:1]([O:3][C:4](=[O:13])[C:5]([C:6]1[CH:11]=[CH:10][N:9]=[C:8]([Br:12])[CH:7]=1)([CH2:28][OH:29])[CH2:14][OH:15])[CH3:2]

참가 물질

6

반응물 4

HCID 712FormaldehydeHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 131278(R)-camphorsulfonic acidHCID 23106708Ethyl 2-(2-bromopyridin-4-yl)acetate

생성물 1

HCID 866680414-Pyridineacetic acid, 2-bromo-α,α-bis(hydroxymethyl)-, ethyl ester

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To an ice cooled stirred mixture of (2-bromo-pyridin-4-yl)-acetic acid ethyl ester (40.0 g, 163.93 mmol) and paraformaldehyde (9.84 g, 327.8 mmol) in dry DCM was added 1,8-diazabicyclo[5.4.0]undec-7-ene (1.49 g, 1.49 ml, 9.83 mmol) and stirred for 2 h. Reaction mixture was treated with (1R)-(−)-10-camphor sulphonic acid (2.283 g, 9.83 mmol) at 0° C. and the organic layer was washed with brine and dried over anhydrous Na2SO4. Concentration of organic layer afforded gummy oily material. The crude compound was purified over triethyl amine treated silicagel using 5-8% methanol in DCM as eluent furnished title compound as a brown liquid. Yield=20.0 g (40%). TLC (30% ethyl acetate in hexane) Rf=0.06; LCMS: RtH7=0.191; [M+1]+=303.9 and 305.8; HPLC RtH9=6.019 min (43%); 1H NMR (400 MHz, CDCl3): δ 8.36-8.31 (m, 1H), 7.34-7.25 (m, 1H), 6.37-6.33 (m, 1H), 4.6 (d, 1H), 4.14-4.08 (m, 2H), 4.04-3.91 (m, 4H), 1.13 (t, 3H).

후처리

  1. stirringstirred for 2 h
  2. customReaction mixture
  3. washthe organic layer was washed with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. customConcentration of organic layer afforded gummy oily material
  6. customThe crude compound was purified over triethyl amine treated silicagel

출처 및 근거

ORD 기록
ord-90515817d5e94f26a565e9cd5b2fe75f
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08637508B2

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