Cesium fluoride → 3-Amino-5-ethynyl N (2 (2 (2 methoxyethoxy)ethoxy)ethyl)benzamide

HRID 1423260Notes

Reaction equation

HRID 1423260 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:18]=[C:19]([C:21]#[C:22][Si](C(C)C)(C(C)C)C(C)C)[CH:20]=1)[C:5]([NH:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12][O:13][CH2:14][CH2:15][O:16][CH3:17])=[O:6].[F-].[Cs+]>CC#N.C(Cl)Cl>[NH2:1][C:2]1[CH:3]=[C:4]([CH:18]=[C:19]([C:21]#[CH:22])[CH:20]=1)[C:5]([NH:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12][O:13][CH2:14][CH2:15][O:16][CH3:17])=[O:6]

Participants

5

Reactant 2

HCID 25953Cesium fluoride2×HCID 904225223-Amino-N-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)-5-((triisopropylsilyl)ethynyl)benzamide

Product 1

HCID 904331363-Amino-5-ethynyl N (2 (2 (2 methoxyethoxy)ethoxy)ethyl)benzamide

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To the product from step (iii) above (1200 g, 2.59 mol) in MeCN (8.8 L) was added CsF (433.6 g, 2.85 mol). The reaction was stirred at RT overnight, after which HPLC analysis showed 1.7% product, 97.4% starting material. Additional CsF (420 g, 2.76 mol) was charged and the reaction stirred at RT overnight, whereupon HPLC analysis revealed 91.0% product, 4.4% starting material. The mixture was filtered and the filtrate concentrated in vacuo to give material which was 92.5% product, 0.7% starting material by HPLC. The residue was dissolved in DCM (3 L) and EtOAc (3 L), before being split into two equal portions. Each portion was passed through a silica pad (1.6 kg), eluting with EtOAc (50 L). The filtrates were combined and concentrated in vacuo. The crude material was washed with heptane (2×4 L) to remove silyl impurities. A total of 719 g of sub-title compound was isolated (83% assay by 1H NMR, 75% active yield, 597 g active).

Workup

  1. stirringthe reaction stirred at RT overnight, whereupon HPLC analysis
  2. filtrationThe mixture was filtered
  3. concentrationthe filtrate concentrated in vacuo
  4. customto give material which
  5. customEtOAc (3 L), before being split into two equal portions
  6. washeluting with EtOAc (50 L)
  7. concentrationconcentrated in vacuo
  8. washThe crude material was washed with heptane (2×4 L)
  9. customto remove silyl impurities

Sources & evidence

ORD record
ord-ba9376e63eb847178a5864ff4d2272f6
Source dataset
uspto-grants-2015_01
Patent number
US08927563B2

Reaction notes

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