Nitrogen → 2-Fluoro-5-(thiazol-2-yl)benzonitrile

HRID 1891446Notes

Reaction equation

HRID 1891446 reaction equation
Br[C:2]1[S:3][CH:4]=[CH:5][N:6]=1.[C:7]([C:9]1[CH:10]=[C:11](B(O)O)[CH:12]=[CH:13][C:14]=1[F:15])#[N:8].C([O-])([O-])=O.[K+].[K+].N#N>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.COCCOC.O>[F:15][C:14]1[CH:13]=[CH:12][C:11]([C:2]2[S:3][CH:4]=[CH:5][N:6]=2)=[CH:10][C:9]=1[C:7]#[N:8]

Participants

7

Reactant 4

HCID 947NitrogenHCID 11430Potassium CarbonateHCID 764302-BromothiazoleHCID 27579643-Cyano-4-fluorophenylboronic acid

Product 1

HCID 583671252-Fluoro-5-(thiazol-2-yl)benzonitrileYield 71%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

A solution of 2-bromothiazole (25 g, 153.4 mmol), (3-cyano-4-fluorophenyl)boronic acid (25.3 g, 153.3 mmol), K2CO3 (63.6 g, 460 mmol) and 3:1 DME/H2O (205 mL) was purged with N2 for 1 h before the addition of Pd(PPh3)4 (9.2 g, 7.9 mmol). The mixture was further degassed with N2 for 5 min and then heated to 85° C. for 7 h under N2. Upon cooling, the reaction mixture was diluted with EA (250 mL), washed with water (200 mL) and brine (200 mL), and dried over MgSO4. The reaction mixture was filtered and concentrated to give beige solid. The crude product was purified by recrystallization from 20% EA/hexanes to afford 22 g (71%) of 2-fluoro-5-(thiazol-2-yl)benzonitrile THZ INT-1 as a pale yellow solid. LCMS-ESI (m/z) calculated for C10H5FN2S: 204.2; found 205.0 [M+H]+, tR=3.26 min. 1H NMR (400 MHz, CDCl3) δ 8.21-8.16 (m, 1H), 8.15-8.08 (m, 1H), 7.86-7.81 (m, 1H), 7.36-7.32 (m, 1H), 7.27-7.21 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 164.31, 162.22, 143.73, 132.68, 131.28, 128.34, 119.94, 116.98, 113.10.

Workup

  1. customThe mixture was further degassed with N2 for 5 min
  2. temperatureUpon cooling
  3. additionthe reaction mixture was diluted with EA (250 mL)
  4. washwashed with water (200 mL) and brine (200 mL)
  5. dry with materialdried over MgSO4
  6. filtrationThe reaction mixture was filtered
  7. concentrationconcentrated
  8. customto give beige solid
  9. customThe crude product was purified by recrystallization from 20% EA/hexanes

Sources & evidence

ORD record
ord-072563af10114a148169a8008480606f
Source dataset
uspto-grants-2013_08
Patent number
US08507538B2

Reaction notes

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