Sodium Hydroxide → 1-(3-Fluorophenyl)-3,4-dihydroisoquinoline

HRID 84132

Reaction equation

HRID 84132 reaction equation
[C:1]1([CH2:7][CH2:8][NH:9][C:10](=O)[C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.P(Cl)(Cl)(Cl)=O.[OH-].[Na+]>C1(C)C(C)=CC=CC=1>[F:17][C:13]1[CH:12]=[C:11]([C:10]2[C:6]3[C:1](=[CH:2][CH:3]=[CH:4][CH:5]=3)[CH2:7][CH2:8][N:9]=2)[CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 14812Phosphorus oxide (P4O10)HCID 24813Phosphorus oxychlorideHCID 7627373-fluoro-N-(2-phenylethyl)benzamide

Product 1

HCID 149989031-(3-Fluorophenyl)-3,4-dihydroisoquinoline

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent

Procedure

289.0 g (1.19 mol) of N-phenylethyl-3-fluorobenzamide were dissolved in 1000 ml of xylene and admixed at 90° C. in portions with 202.7 g (1.43 mol, 1.2 eq.) of phosphorus pentoxide. Subsequently, 326.8 ml (3.57 mol, 3.0 eq.) of phosphorus oxychloride were added dropwise. The mixture was heated under reflux for 4 h. The reaction solution was subsequently poured while hot onto ice and adjusted cautiously to pH=12 with solid NaOH with ice cooling. The precipitate was extracted three times with 500 ml of toluene, dried over MgSO4 and concentrated under reduced pressure to a highly viscous oil which later crystallizes. 267.41 g are obtained with a purity of approx. 99%, corresponding to 99.8% of theory.

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 4 h
  3. additionThe reaction solution was subsequently poured while hot onto ice
  4. extractionThe precipitate was extracted three times with 500 ml of toluene
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated under reduced pressure to a highly viscous oil which
  7. customlater crystallizes
  8. custom267.41 g are obtained with a purity of approx. 99%, corresponding to 99.8% of theory

Sources & evidence

ORD record
ord-b9bb6f05cffe41df884aca98ba12e310
Source dataset
uspto-grants-2014_09
Patent number
US08846920B2

Linked notes

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