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

HRID 474070ノート

反応式

HRID 474070 の反応式
[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]

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-90515817d5e94f26a565e9cd5b2fe75f
出典データセット
uspto-grants-2014_01
特許番号
US08637508B2

反応ノート

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