Reaction #9711

Reaction equation

methyl (1R,2R)-2-[(3′-fluoro-4′-{[6-(trifluoromethoxy)-1,3-benzothiazol-2-yl]amino}-1,1′-biphenyl-4-yl)carbonyl]cyclopentanecarboxylate

tert-butyl (1R,2R)-2-(bromobenzoyl)-cyclopentanecarboxylate

N-(4-bromo-2-fluorophenyl)-N-(6-fluoro-1,3-benzothiazol-2-yl)amine

→

tert-Butyl (1R,2R)-2-({3′-fluoro-4′-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentanecarboxylate

desired product

Yield 77.0%

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

Yield 77.0%

Solvents

TFA

CH2Cl2

Conditions

Workup

1. 1
   OtherAfter the solvent was removed by rotary evaporation, 50 mL EtOAc and 50 mL water
2. 2
   workup.ADDITIONwere added
3. 3
   OtherThe organic layer was separated
4. 4
   Washwashed with 50 mL water
5. 5
   Dryingdried over Na2SO4
6. 6
   OtherAfter the solvent was removed by rotary evaporation, 5 mL EtOAc
7. 7
   workup.ADDITIONwas added to the residue
8. 8
   OtherThe precipitate that formed
9. 9
   Filtrationwas collected by filtration

Procedure

tert-Butyl (1R,2R)-2-({3′-fluoro-4′-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentanecarboxylate was prepared from tert-butyl (1R,2R)-2-(bromobenzoyl)-cyclopentanecarboxylate and N-(4-bromo-2-fluorophenyl)-N-(6-fluoro-1,3-benzothiazol-2-yl)amine in a similar manner to that described above for methyl (1R,2R)-2-[(3′-fluoro-4′-{[6-(trifluoromethoxy)-1,3-benzothiazol-2-yl]amino}-1,1′-biphenyl-4-yl)carbonyl]cyclopentanecarboxylate. A solution of the tert-butyl ester (1.5 g, 2.81 mmol) in 2.0 mL TFA and 10 mL CH2Cl2 was stirred at rt overnight. After the solvent was removed by rotary evaporation, 50 mL EtOAc and 50 mL water were added. The organic layer was separated, washed with 50 mL water, and then dried over Na2SO4. After the solvent was removed by rotary evaporation, 5 mL EtOAc was added to the residue, followed by 5 mL hexanes. The precipitate that formed was collected by filtration to afford the desired product as a light yellow solid (1.0 g, 77%, 95.2% ee). 1H NMR (400 MHz, DMSO-d6) δ 12.20 (br s, 1 H), 10.50 (bs, 1 H), 8.70 (t, 1 H), 7.60–8.10 (m, 8 H), 7.20 (t, 1 H), 4.10 (m, 1 H), 3.20 (m, 1 H), 2.20 (m, 1 H), 2.00 (m, 1 H), 1.50–1.90 (m, 4 H); LC-MS m/z 479.3 (MH+), ret. time 3.64 min.

Source