Boron tribromide → 3-(3-Fluoro-4-hydroxyphenyl)-7-hydroxy-1-naphthonitrile

HRID 226271Notes

Reaction equation

HRID 226271 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:11]=[C:12]([C:22]#[N:23])[C:13]3[C:18]([CH:19]=2)=[CH:17][CH:16]=[C:15]([O:20]C)[CH:14]=3)[CH:5]=[CH:6][C:7]=1[O:8]C.B(Br)(Br)Br>>[F:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:11]=[C:12]([C:22]#[N:23])[C:13]3[C:18]([CH:19]=2)=[CH:17][CH:16]=[C:15]([OH:20])[CH:14]=3)[CH:5]=[CH:6][C:7]=1[OH:8]

Participants

3

Reactant 2

HCID 25134Boron tribromideHCID 116881113-(3-Fluoro-4-methoxyphenyl)-7-methoxy-1-naphthonitrile

Product 1

HCID 61026913-(3-Fluoro-4-hydroxyphenyl)-7-hydroxy-1-naphthonitrileYield 73%

Procedure

In a highly preferred process of this invention, 3-Bromo-7-methoxy-1-naphthonitrile (6) is coupled with 3-fluoro-4-methoxyphenylboronic acid, which is commercially available, under the well-known Suzuki condition using sodium bicarbonate and catalytic amount of dichloro-bis(triphenylphosphine) palladium (II) in a mixture of water and 1,2-dimethoxyethane to give 3-(3-fluoro-4-methoxyphenyl)-7-meythoxy-1-naphthonitrile (8); typically the yield is approximately 98% with about 95%+HPLC purity. Finally, in this highly preferred process 3-(3-fluoro-4-methoxyphenyl)-7-methoxy-1-naphthonitrile (8) is demethylated using boron tribromide at about 83° C. and recrystallized from a mixture of water and ethanol to give 3-(3-fluoro-4-hydroxyphenyl)-7-hydroxy-1-naphthonitrile (1), typically in about 73% yield with 99%+HPLC purity.

Workup

  1. customat about 83° C.
  2. customrecrystallized from a mixture of water and ethanol

Sources & evidence

ORD record
ord-baa60cb246234bcc9bbdce8e3f195844
Source dataset
uspto-grants-2009_07
Patent number
US07557237B2

Reaction notes

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