Hydrochloric Acid → [6-Fluoro-3-methyl-4-(4-methyl-benzyl)-naphthalen-2-yl]-acetic acid

HRID 1644750Notes

Reaction equation

HRID 1644750 reaction equation
C[O:2][C:3](=[O:25])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:24])[CH:11]=2)[CH:6]=1.O.[OH-].[Li+].Cl>O1CCCC1.O>[F:24][C:10]1[CH:11]=[C:12]2[C:7](=[CH:8][CH:9]=1)[CH:6]=[C:5]([CH2:4][C:3]([OH:25])=[O:2])[C:14]([CH3:15])=[C:13]2[CH2:16][C:17]1[CH:18]=[CH:19][C:20]([CH3:23])=[CH:21][CH:22]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 59350825[6-Fluoro-3-methyl-4-(4-methyl-benzyl)-naphthalen-2-yl]-acetic acid methyl ester

Product 1

HCID 46206526[6-Fluoro-3-methyl-4-(4-methyl-benzyl)-naphthalen-2-yl]-acetic acidYield 60.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of [6-fluoro-3-methyl-4-(4-methyl-benzyl)-naphthalen-2-yl]-acetic acid methyl ester (140.8 mg, 0.419 mmol) in tetrahydrofuran (14 mL) was treated with a warm solution of lithium hydroxide monohydrate (175.8 mg, 4.19 mmol) in water (3.5 mL). The reaction mixture was stirred at room temperature for 20 hours, diluted with water, acidified with aqueous 3.0 N HCl and extracted with ethyl acetate. The ethyl acetate layers were combined, washed with brine, dried (MgSO4), filtered and concentrated. Purification by reverse phase HPLC gave 81.7 mg (60%) of [6-fluoro-3-methyl-4-(4-methyl-benzyl)-naphthalen-2-yl]-acetic acid as a white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 12.43 (br. s, 1 H), 7.91 (dd, J=8.7, 6.3 Hz, 1 H), 7.74 (s, 1 H), 7.62 (dd, J=12.1, 1.8 Hz, 1 H), 7.33 (td, J=8.7, 1.8 Hz, 1 H), 7.03 (d, J=7.8 Hz, 2 H), 6.92 (d, J=7.8 Hz, 2 H), 4.40 (s, 2H), 3.82 (s, 2 H), 2.32 (s, 3 H), 2.21 (s, 3 H). HRMS (ES−) cald. for C21H19FO2 [(M−H)−] 321.1296, obsd. 321.1294.

Workup

  1. extractionextracted with ethyl acetate
  2. washwashed with brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by reverse phase HPLC

Sources & evidence

ORD record
ord-fd8a2407489e45318b160a9c883ed7c8
Source dataset
uspto-grants-2012_02
Patent number
US08124629B2

Reaction notes

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