Reaction #44378

ord-a10d245fc92c400e98ec2b3607f30896

Reaction equation

C[C@H](Oc1ccc(Cl)cc1B(O)O)C(=O)O
product
C[C@H](Oc1ccc(Cl)cc1B(O)O)C(=O)O
(2S)-2-(2-borono-4-chlorophenoxy)-propanoic acid
CC(C)N(C(=O)c1ccc(Br)cc1F)C(C)C
product
CC(C)N(C(=O)c1ccc(Br)cc1F)C(C)C
4-bromo-2-fluoro-N,N-bis(1-methylethyl)-benzamide
O=C([O-])[O-].[Na+].[Na+]
sodium carbonate
→
CC(C)N(C(=O)c1ccc(-c2cc(Cl)ccc2O[C@@H](C)C(=O)O)cc1F)C(C)C
title compound
CC(C)N(C(=O)c1ccc(-c2cc(Cl)ccc2O[C@@H](C)C(=O)O)cc1F)C(C)C
(2S)-2-[[4′-[[bis(1-methylethyl)amino]carbonyl]-5-chloro-3′-fluoro[1,1′-biphenyl]-2-yl]oxy]-propanoic acid

Reactants

C[C@H](Oc1ccc(Cl)cc1B(O)O)C(=O)O
product
C[C@H](Oc1ccc(Cl)cc1B(O)O)C(=O)O
(2S)-2-(2-borono-4-chlorophenoxy)-propanoic acid
CC(C)N(C(=O)c1ccc(Br)cc1F)C(C)C
product
CC(C)N(C(=O)c1ccc(Br)cc1F)C(C)C
4-bromo-2-fluoro-N,N-bis(1-methylethyl)-benzamide
O=C([O-])[O-].[Na+].[Na+]
sodium carbonate

Reagents

[Cl][Pd][Cl].[Fe+2].c1ccc(P(c2ccccc2)[c-]2cccc2)cc1.c1ccc(P(c2ccccc2)[c-]2cccc2)cc1
Pd(dppf)Cl2

Solvents

C1COCCO1
dioxan

Conditions

Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    Temperatureheated
  2. 2
    Temperatureat reflux for 24 h
  3. 3
    Filtrationfiltered (hyflo)
  4. 4
    ConcentrationThe filtrate was concentrated in vacuo
  5. 5
    Otherpurified by reverse phase HPLC

Procedure

The product of step c) (200 mg), the product of step d) (200 mg), Pd(dppf)Cl2 (60 mg), sodium carbonate (350 mg) and dioxan (5 ml) were charged to a flask and heated at reflux for 24 h, then cooled to room temp and filtered (hyflo). The filtrate was concentrated in vacuo, then purified by reverse phase HPLC to give the title compound. Yield 22 mg

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US07737135B2uspto-grants-2010_06