Reaction #9706

Reaction equation

(1R,2R)-2-(4-bromobenzoyl)cyclopentanecarboxylic acid

Cs2CO3

N-(4-iodo-2-fluorophenyl)-6-chloro-1,3-benzothiazol-2-amine

bis(pinacolato)diboron

KOAc

→

desired product

Yield 60.0%

(1R,2R)-2-({4′-[(6-Chloro-1,3-benzothiazol-2-yl)amino]-3′-fluoro-1,1′-biphenyl-4-yl}carbonyl)cyclopentanecarboxylic acid

Yield 60.0%

Solvents

water

DMF

Conditions

Workup

1. 1
   Otherwas degassed
2. 2
   Otherby bubbling a flow of nitrogen for 30 minutes
3. 3
   TemperatureAfter the mixture was cooled to rt
4. 4
   Temperaturethe reaction mixture was heated at 85° C. under nitrogen for 3 h
5. 5
   TemperatureThe reaction mixture was cooled to rt
6. 6
   FiltrationAfter the mixture was filtered through a pad of Celite®, 1 N HCl
7. 7
   workup.ADDITIONwas added to the filtrate
8. 8
   OtherThe solid that formed
9. 9
   Filtrationwas collected by filtration
10. 10
    workup.DISSOLUTIONdissolved in EtOAc (50 mL)
11. 11
    Dryingthe resulting solution was dried over Na2SO4
12. 12
    OtherRemoval of solvent
13. 13
    Otherdrying in vacuo

Procedure

A suspension of N-(4-iodo-2-fluorophenyl)-6-chloro-1,3-benzothiazol-2-amine (200 mg, 0.49 mmol), bis(pinacolato)diboron (130 mg, 0.52 mmol), KOAc (150 mg, 1.48 mmol), and PdCl2(dppf) (30 mg, 0.04 mmol) in DMF (5.0 mL) was degassed by bubbling a flow of nitrogen for 30 minutes. The reaction mixture was heated under nitrogen at 85° C. for 3 h. After the mixture was cooled to rt, (1R,2R)-2-(4-bromobenzoyl)cyclopentanecarboxylic acid (140 mg, 0.49 mmol, >99% ee), Cs2CO3 (400 mg, 1.23 mmol) and PdCl2(dppf) (30 mg, 0.04 mmol) were added, and the reaction mixture was heated at 85° C. under nitrogen for 3 h. TLC analysis showed little starting materials remaining. The reaction mixture was cooled to rt, and diluted with water (50 mL). After the mixture was filtered through a pad of Celite®, 1 N HCl was added to the filtrate to adjust the acidity to pH<3. The solid that formed was collected by filtration, then dissolved in EtOAc (50 mL), and the resulting solution was dried over Na2SO4. Removal of solvent and drying in vacuo provided the desired product (120 mg, 60%, >99% ee). LC-MS m/z 495.3 (MH+), retention time 4.01 min.

Source