Hydrochloric Acid → 2-Tert-butoxy-2-[9-[(4-fluorophenyl)methyl]-2-methyl-1-oxo-4-(p-tolyl)pyrido[3,4-b]indol-3-yl]acetic acid

HRID 1473263Notes

Reaction equation

HRID 1473263 reaction equation
[C:1]([O:5][CH:6]([C:11]1[N:31]([CH3:32])[C:30](=[O:33])[C:14]2[N:15]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)[C:16]3[C:21]([C:13]=2[C:12]=1[C:34]1[CH:39]=[CH:38][C:37]([CH3:40])=[CH:36][CH:35]=1)=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:7]([O:9]C)=[O:8])([CH3:4])([CH3:3])[CH3:2].[Li+].[OH-].Cl>O1CCCC1.CO>[C:1]([O:5][CH:6]([C:11]1[N:31]([CH3:32])[C:30](=[O:33])[C:14]2[N:15]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)[C:16]3[C:21]([C:13]=2[C:12]=1[C:34]1[CH:35]=[CH:36][C:37]([CH3:40])=[CH:38][CH:39]=1)=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 89462821HCID 89462821, compound

Product 1

HCID 715364972-Tert-butoxy-2-[9-[(4-fluorophenyl)methyl]-2-methyl-1-oxo-4-(p-tolyl)pyrido[3,4-b]indol-3-yl]acetic acidYield 32%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A solution of methyl 2-(tert-butoxy)-2-(9-(4-fluorobenzyl)-2-methyl-1-oxo-4-(p-tolyl)-2,9-dihydro-1H-pyrido[3,4-b]indol-3-yl)acetate (30 mg, 0.055 mmol) in Tetrahydrofuran (THF) (1 mL) and Methanol (1 mL) was treated with 2M LiOH (1 mL, 2.000 mmol) and then heated at 70° C. for 1 hour. The mixture was cooled to 0° C., treated with HCl (1M) until pH <2 and then extracted with ethyl acetate. The combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by reverse phase chromatography (10-90% MeCN/H2O-0.1% TFA, 12 min) to afford 2-(tert-butoxy)-2-(9-(4-fluorobenzyl)-2-methyl-1-oxo-4-(p-tolyl)-2,9-dihydro-1H-pyrido[3,4-b]indol-3-yl)acetic acid (9.2 mg, 0.017 mmol, 32% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) ppm 13.35 (s, 1H), 7.73-7.66 (m, 1H), 7.50-7.32 (m, 7H), 7.19-7.09 (m, 2H), 6.98-6.89 (m, 1H), 6.49-6.51 (m, 1H), 6.14 (s, 2H), 5.17 (s, 1H), 3.66 (m, 3H), 2.49 (s, 3H), 0.97 (s, 9H); LCMS (m/z) ES+=527 (M+1).

Workup

  1. temperatureThe mixture was cooled to 0° C.
  2. extractionextracted with ethyl acetate
  3. washThe combined extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by reverse phase chromatography (10-90% MeCN/H2O-0.1% TFA, 12 min)

Sources & evidence

ORD record
ord-99152133d7944e9b85cb2cef1418bfbf
Source dataset
uspto-grants-2015_04
Patent number
US09012642B2

Reaction notes

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