Trifluoroacetic acid → HCID 86703754, compound

HRID 1849869Notes

Reaction equation

HRID 1849869 reaction equation
[CH:1]1([C:4]2[C:5]([O:18][CH2:19][C:20]3([CH3:26])[CH2:25][CH2:24][CH:23]=[CH:22][CH2:21]3)=[CH:6][C:7]([F:17])=[C:8]([CH:16]=2)[C:9]([O:11]C(C)(C)C)=[O:10])[CH2:3][CH2:2]1.FC(F)(F)C(O)=O>ClCCl>[CH:1]1([C:4]2[C:5]([O:18][CH2:19][C:20]3([CH3:26])[CH2:25][CH2:24][CH:23]=[CH:22][CH2:21]3)=[CH:6][C:7]([F:17])=[C:8]([CH:16]=2)[C:9]([OH:11])=[O:10])[CH2:2][CH2:3]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86703755HCID 86703755, compound

Product 1

HCID 86703754HCID 86703754, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 5-cyclopropyl-2-fluoro-4-((1-methylcyclohex-3-en-1-yl)methoxy)benzoate (0.041 g, 0.11 mmol) in dichloromethane (2 mL), was added trifluoroacetic acid (2 mL). The reaction mixture was stirred at room temperature for 1 hour and then concentrated in vacuo to afford 5-cyclopropyl-2-fluoro-4-((1-methylcyclohex-3-en-1-yl)methoxy)benzoic acid (0.033 g, 0.11 mmol) which was used directly in the next step. This compound was dissolved in tetrahydrofuran (2 mL) under an atmosphere of nitrogen and carbonyldiimidazole (0.024 g, 0.15 mmol) was added to the solution and the reaction mixture was stirred at 70° C. for 1 hour. The mixture was cooled to ambient temperature and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.04 mg, 0.17 mmol) was added, followed by cyclopropanesulfonamide (0.021 mg, 0.170 mmol) and stirring continued at ambient temperature for 18 hours. 5% aqueous hydrochloric acid solution (0.15 mL) was added and the mixture was concentrated and purified by column chromatography (0 to 30% ethyl acetate in hexanes) to afford the title compound (0.012 g, 24%) as a colorless solid: 1H NMR (300 MHz, CDCl3) δ 9.18-8.28 (br, 1H), 7.60 (s, 1H), 6.56 (d, J=14.4 Hz, 1H), 5.75-5.57 (m, 2H), 3.76 (d, J=8.5 Hz, 1H), 3.69 (d, J=8.6 Hz, 1H), 3.17-3.00 (m, 1H), 2.18-1.95 (m, 4H), 1.95-1.81 (m, 1H), 1.78-1.63 (m, 1H), 1.57-1.36 (m, 3H), 1.23 (s, 3H), 1.18-1.05 (m, 2H), 0.96-0.85 (m, 2H), 0.68-0.59 (m, 2H); MS (ES+) m/z 408.2 (M+1); MS (ES−) m/z 406.2 (M−1).

Workup

  1. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b4b98d1a2c624e2492f0c6fd1be6667f
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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