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

HRID 538331Notes

Reaction equation

HRID 538331 reaction equation
[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]

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 131278(R)-camphorsulfonic acidHCID 23106708HCID 23106708, compound

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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): b 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).

Workup

  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

Sources & evidence

ORD record
ord-3b40c12647fc4be69376b453425b1e69
Source dataset
uspto-grants-2014_10
Patent number
US08865712B2

Reaction notes

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