Hydrochloric Acid → 7-(4-((2-(4-chlorophenyl)cyclopropyl)carbamoyl)phenoxy)-6-cyano-3,4-dihydro-2H-chromene-4-carboxylic acid

HRID 1048064Notes

Reaction equation

HRID 1048064 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:10][CH:9]2[NH:11][C:12]([C:14]2[CH:36]=[CH:35][C:17]([O:18][C:19]3[CH:28]=[C:27]4[C:22]([CH:23]([C:29]([O:31]C)=[O:30])[CH2:24][CH2:25][O:26]4)=[CH:21][C:20]=3[C:33]#[N:34])=[CH:16][CH:15]=2)=[O:13])=[CH:4][CH:3]=1.O[Li].O.Cl>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:10][CH:9]2[NH:11][C:12]([C:14]2[CH:15]=[CH:16][C:17]([O:18][C:19]3[CH:28]=[C:27]4[C:22]([CH:23]([C:29]([OH:31])=[O:30])[CH2:24][CH2:25][O:26]4)=[CH:21][C:20]=3[C:33]#[N:34])=[CH:35][CH:36]=2)=[O:13])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 46221109methyl 7-(4-((2-(4-chlorophenyl)cyclopropyl) carbamoyl)phenoxy)-6-cyano-3,4-dihydro-2H-chromene-4-carboxylate

Product 1

HCID 445400167-(4-((2-(4-chlorophenyl)cyclopropyl)carbamoyl)phenoxy)-6-cyano-3,4-dihydro-2H-chromene-4-carboxylic acidYield 95.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

methyl 7-(4-((2-(4-chlorophenyl)cyclopropyl)carbamoyl)phenoxy)-6-cyano-3,4-dihydro-2H-chromene-4-carboxylate (50.7 mg, 0.101 mmol) was dissolved in THF (3 ml). A 1M solution of LiOH—H2O (0.202 ml, 0.202 mmol) was added and the mixture was stirred for 17 hours at ambient temperature. HCl (4M in dioxane) (0.0756 ml, 0.302 mmol) was added to the mixture. The solution was stirred additional 30 minutes and concentrated. The residue was purified on silica gel (MeOH in dichloromethane with 1% acetic acid gradient) to provide 47 mg of the title compound as a solid (95%). MS (apci) m/z=486.7 (M−H).

Workup

  1. stirringThe solution was stirred additional 30 minutes
  2. concentrationconcentrated
  3. customThe residue was purified on silica gel (MeOH in dichloromethane with 1% acetic acid gradient)

Sources & evidence

ORD record
ord-62a45cd2daa14635b7f2114280abc7b4
Source dataset
uspto-grants-2013_10
Patent number
US08569522B2

Reaction notes

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