Hydrochloric Acid → HCID 72548654, compound

HRID 1849860Notes

Reaction equation

HRID 1849860 reaction equation
[CH:1]1([C:4]2[C:5]([O:14][CH2:15][CH:16]3[CH2:21][CH2:20][CH2:19][CH2:18][CH:17]3[CH3:22])=[CH:6][C:7]([F:13])=[C:8]([CH:12]=2)[C:9]([OH:11])=O)[CH2:3][CH2:2]1.C(N1C=CN=C1)(N1C=CN=C1)=O.N12CCCN=C1CCCCC2.[CH:46]1([S:49]([NH2:52])(=[O:51])=[O:50])[CH2:48][CH2:47]1.Cl>O1CCCC1>[CH:1]1([C:4]2[C:5]([O:14][CH2:15][CH:16]3[CH2:21][CH2:20][CH2:19][CH2:18][CH:17]3[CH3:22])=[CH:6][C:7]([F:13])=[C:8]([CH:12]=2)[C:9]([NH:52][S:49]([CH:46]2[CH2:48][CH2:47]2)(=[O:51])=[O:50])=[O:11])[CH2:2][CH2:3]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 15765418CyclopropanesulfonamideHCID 86703747HCID 86703747, compound

Product 1

HCID 72548654HCID 72548654, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a stirred solution of 5-cyclopropyl-2-fluoro-4-((2-methylcyclohexyl)-methoxy)benzoic acid (0.093 g, 0.305 mmol) in tetrahydrofuran (2 mL) under an atmosphere of nitrogen was added carbonyldiimidazole (0.074 g, 0.457 mmol) and the reaction mixture was stirred at 70° C. for 1 hour. The mixture was cooled to room temperature and 1,8-Diazabicyclo[5.4.0]undec-7-ene (0.07 mL, 0.45 mmol) was added followed by cyclopropanesulfonamide (0.06 mg, 0.52 mmol). Stirring was continued at ambient temperature for 18 hours. 5% aqueous hydrochloric acid solution (0.15 mL) was added and the mixture was concentrated and directly purified by column chromatography (0 to 30% ethyl acetate in hexanes) to afford the title compound (0.05 g, 43%) as a colorless solid: 1H NMR (300 MHz, CDCl3) δ 8.79-8.58 (m, 1H), 7.56 (d, J=9.1 Hz, 1H), 6.57 (d, J=14.5 Hz, 1H), 3.87 (dd, J=7.0, 2.7 Hz, 2H), 3.08 (tt, J=8.1, 8.1, 4.8, 4.8 Hz, 1H), 2.21-1.93 (m, 3H), 1.76-1.35 (m, 9H), 1.13 (dq, J=6.20, 6.08, 1.31 Hz, 2H), 0.98-0.86 (m, 5H), 0.68-0.59 (m, 2H); MS (ES+) m/z 410.1 (M+1); MS (ES−) m/z 408.2 (M−1).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. stirringStirring
  3. waitwas continued at ambient temperature for 18 hours
  4. concentrationthe mixture was concentrated
  5. customdirectly purified by column chromatography (0 to 30% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-bfeb550ed0064823aea7ad032888508a
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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