Water → 4-Chloro-5-(cyclopentyloxy)-2-fluorobenzenamine

HRID 1684316Notes

Reaction equation

NC1C(F)=CC(Cl)=C(O[C:9](=O)[O:10][C:11]2[CH:16]=[C:15]([NH2:17])[C:14]([F:18])=[CH:13][C:12]=2[Cl:19])C=1.CS(O[CH:28]1[CH2:32]C[CH2:30][CH2:29]1)(=O)=O.[OH-].[Na+].O>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[Cl:19][C:12]1[C:11]([O:10][CH:9]2[CH2:30][CH2:29][CH2:28][CH2:32]2)=[CH:16][C:15]([NH2:17])=[C:14]([F:18])[CH:13]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A round-bottomed flask (50 cc) was charged with bis(5-amino-2-chloro-4-fluorophenyl)carbonate (1.50 g, 4.29 mmol), cyclopentyl methanesulfonate (1.50 g, 9.15 mmol) and tetrabutylammonium bromide (70 mg, 0.22 mmol) to prepare a solution in toluene (12 mL). Subsequently, 48% sodium hydroxide in aqueous solution (6 mL) was added slowly and the mixture was stirred under heating at 80° C. for 3 h. After completion of the reaction, the reaction mixture was cooled to room temperate and water (15 mL) was added, followed by extraction with toluene (10 mL×2). The organic layers were combined and washed with water (10 mL×2). The solvent was distilled off under vacuum from the resulting toluene solution, thereby giving 4-chloro-5-cyclopentyloxy-2-fluoroaniline (1.94 g, 8.45 mmol; yield=98.4%; purity on HPLC=94.3%). BP: 143°-145° C./1.5 mmHg 1H-NMR(CDCl3,TMS,ppm): δ1.40-2.00(8H,m), 3.72(2H,s), 4.76(1H,m), 6.39(1H,d,JHF =9.0Hz), 7.04(1H,d,JHF =11.0Hz). IR (neat, cm-1): 3500, 3400, 1630, 1510, 1420, 1245, 1185.

Workup

customAfter completion of the reaction
additionwas added
extractionfollowed by extraction with toluene (10 mL×2)
washwashed with water (10 mL×2)
distillationThe solvent was distilled off under vacuum from the resulting toluene solution

Sources & evidence

ORD record: ord-60d17a1266324d0d8ed8c5b0b616e803
Source dataset: uspto-grants-1997_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05639915

Reaction notes

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