Sodium Hydroxide → 2-(4-Cyano-3-methylphenyl)-3-cyclopentenyl-2,3,3a,4-tetrahydrochromeno[4,3-c]pyrazole-7-carboxylic acid

HRID 505743Notes

Reaction equation

HRID 505743 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH:13]([C:14]3[CH2:18][CH2:17][CH2:16][CH:15]=3)[CH:12]3[CH2:19][O:20][C:21]4[CH:22]=[C:23]([C:27]([O:29]C)=[O:28])[CH:24]=[CH:25][C:26]=4[C:11]3=[N:10]2)=[CH:5][C:4]=1[CH3:31])#[N:2].[OH-].[Na+]>CO.O1CCCC1>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH:13]([C:14]3[CH2:18][CH2:17][CH2:16][CH:15]=3)[CH:12]3[CH2:19][O:20][C:21]4[CH:22]=[C:23]([C:27]([OH:29])=[O:28])[CH:24]=[CH:25][C:26]=4[C:11]3=[N:10]2)=[CH:5][C:4]=1[CH3:31])#[N:2]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 66723040Methyl 2-(4-cyano-3-methylphenyl)-3-cyclopentenyl-2,3,3a,4-tetrahydrochromeno[4,3-c]pyrazole-7-carboxylate

Product 1

HCID 667227152-(4-Cyano-3-methylphenyl)-3-cyclopentenyl-2,3,3a,4-tetrahydrochromeno[4,3-c]pyrazole-7-carboxylic acidYield 55%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 2-(4-cyano-3-methylphenyl)-3-cyclopentenyl-2,3,3a,4-tetrahydrochromeno[4,3-c]pyrazole-7-carboxylate (125 mg, 0.30 mmol) in methanol (2 mL) and tetrahydrofuran (2 mL) was added 1M aqueous sodium hydroxide (2 mL). The solution was stirred for 20 hours at ambient temperature. The resulting slurry was concentrated to half volume, acidified to pH=2 with 1M hydrochloric acid and collected by vacuum filtration (yellow solid, 66 mg, 55% yield). The title compound was largely present as (±)-(3RS,3aRS)-2-(4-cyano-3-methylphenyl)-3-cyclopentenyl-2,3,3a,4-tetrahydrochromeno[4,3-c]pyrazole-7-carboxylic acid. Reversed-phase HPLC on 4.6×50 mm C-18 column, tR=2.92 minutes (10 to 90% acetonitrile/water over 4 minutes at 4 mL/minute with detection 254 nm, at 20° C.); HRMS Calculated for C24H21N3O3: 400.1656 (M+H)+. Found: 400.1678. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.61-1.87 (m, 2H), 2.03-2.13 (m, 2H), 2.17 (br. s., 2H), 2.39 (s, 3H), 3.83-3.91 (m, 1H), 3.97-4.06 (m, 1H), 4.65 (dd, J=10.20, 5.91 Hz, 1H), 5.44 (d, J=10.47 Hz, 1H), 5.60 (br. s., 1H), 6.86 (br. s., 1H), 7.11 (br. s., 1H), 7.42 (d, J=1.34 Hz, 1H), 7.53 (d, J=8.59 Hz, 1H), 7.56 (dd, J=8.19, 1.48 Hz, 1H), 7.90 (d, J=8.06 Hz, 1H), 13.12 (br. s., 1H).

Workup

  1. concentrationThe resulting slurry was concentrated to half volume
  2. filtrationcollected by vacuum filtration (yellow solid, 66 mg, 55% yield)
  3. customon 4.6×50 mm C-18 column, tR=2.92 minutes (10 to 90% acetonitrile/water over 4 minutes at 4 mL/minute with detection 254 nm, at 20° C.)

Sources & evidence

ORD record
ord-d6ed6b279aab40308d07ed733f7b8ed7
Source dataset
uspto-grants-2010_08
Patent number
US07781428B2

Reaction notes

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