Tetrahydrofuran → 2-(3-(benzyloxy)-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid

HRID 505726Notes

Reaction equation

HRID 505726 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([N:17]2[CH:25]([CH:26]3[CH2:30][CH2:29][CH2:28][CH2:27]3)[CH:24]3[C:19]([C:20]4[CH:34]=[CH:33][C:32]([C:35]([O:37]C)=[O:36])=[CH:31][C:21]=4[CH2:22][CH2:23]3)=[N:18]2)[CH:12]=[CH:13][C:14]=1[C:15]#[N:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O1CCCC1.[OH-].[Na+]>CO>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([N:17]2[CH:25]([CH:26]3[CH2:27][CH2:28][CH2:29][CH2:30]3)[CH:24]3[C:19]([C:20]4[CH:34]=[CH:33][C:32]([C:35]([OH:37])=[O:36])=[CH:31][C:21]=4[CH2:22][CH2:23]3)=[N:18]2)[CH:12]=[CH:13][C:14]=1[C:15]#[N:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 66722631methyl 2-(3-(benzyloxy)-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylate

Product 1

HCID 667228752-(3-(benzyloxy)-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acidYield 93%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of methyl 2-(3-(benzyloxy)-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylate, Example 30, (100 mg, 0.20 mmol), tetrahydrofuran (3 mL), and methanol (1 mL) was treated with 2.5 N sodium hydroxide (1 mL) at room temperature. After 18 hours the mixture was concentrated to one-third of its original volume, diluted with water (3 mL) and treated with 2 N hydrogen chloride (2 mL). The mixture was extracted three times with ethyl acetate, dried over magnesium sulfate, filtered and concentrated to give 2-(3-(benzyloxy)-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid (yellow/orange solid, 90 mg, 0.18 mmol, 93% yield). The title compound was largely present as (±)-(3RS,3aSR)-2-(3-(benzyloxy)-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.03-1.51 (m, 7H), 1.57-1.69 (m, 1H), 1.74-1.89 (m, 1H), 1.95-2.07 (m, 1H), 2.18-2.29 (m, 1H), 2.82-2.96 (m, 1H), 3.03-3.14 (m, 1H), 3.57 (ddd, J=13.70, 9.40, 4.30 Hz, 1H), 4.91 (dd, J=9.53, 5.50 Hz, 1H), 5.31 (q, J=12.35 Hz, 2H), 6.84 (d, J=8.86 Hz, 1H), 6.96 (s, 1H), 7.35 (t, J=7.25 Hz, 1H), 7.40-7.53 (m, 5H), 7.81-7.88 (m, 2H), 8.09 (d, J=8.06 Hz, 1H), 13.03 (s, 1H). ES-MS m/z 492 (M+H).

Workup

  1. concentrationAfter 18 hours the mixture was concentrated to one-third of its original volume
  2. additiondiluted with water (3 mL)
  3. additiontreated with 2 N hydrogen chloride (2 mL)
  4. extractionThe mixture was extracted three times with ethyl acetate
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-5d87cc3b48af425aa5d8288f557000ac
Source dataset
uspto-grants-2010_08
Patent number
US07781428B2

Reaction notes

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