Lithium hydroxide, monohydrate → HCID 71603263, compound

HRID 2363881Notes

Reaction equation

HRID 2363881 reaction equation
C[O:2][C:3](=[O:33])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([CH:16]2[CH2:21][CH2:20][N:19]([C:22](=[O:31])[C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=3[Cl:30])[CH2:18][CH2:17]2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:32])[CH:11]=2)[CH:6]=1.O.[OH-].[Li+]>C1COCC1.O.C(OCC)(=O)C>[Cl:30][C:24]1[CH:25]=[C:26]([Cl:29])[CH:27]=[CH:28][C:23]=1[C:22]([N:19]1[CH2:20][CH2:21][CH:16]([C:13]2[C:12]3[C:7](=[CH:8][CH:9]=[C:10]([F:32])[CH:11]=3)[CH:6]=[C:5]([CH2:4][C:3]([OH:33])=[O:2])[C:14]=2[CH3:15])[CH2:17][CH2:18]1)=[O:31]

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86686920HCID 86686920, compound

Product 1

HCID 71603263HCID 71603263, compoundYield 48.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a colorless solution of {4-[1-(2,4-dichloro-benzoyl)-piperidin-4-yl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid methyl ester (102 mg, 0.21 mmol) in THF (8.0 mL) was added a solution of lithium hydroxide monohydrate (100 mg, 4.2 mmol) in water (2.0 mL) at room temperature. The resulting colorless solution was stirred for 15 hours. The solvent was removed and the aqueous solution after dilution with water was neutralized with 1.0 N aqueous HCl. The resulting white precipitate was collected by filtration and washed with hexanes. After drying in the air, 62 mg of the crude product was isolated as a white solid. The crude product was dissolved in ethyl acetate (˜3 mL) with heating and the resulting solution was diluted with hexanes (˜20 mL). The solution was stored in the freezer for three days and the precipitated solids were collected by filtration and washed with hexanes. After drying in air, {4-[1-(2,4-dichloro-benzoyl)-piperidin-4-yl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid (48 mg, 48%) was isolated as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.42 (br. s, 1H), 7.85-7.97 (m, 1H), 7.81 (br. s, 1H), 7.75 (s, 1H), 7.69 (s, 1H), 7.51-7.63 (m, 1H), 7.41-7.50 (m, 1H), 7.35 (t, J=8.03 Hz, 1H), 4.71 (br. s, 1H), 3.78 (br. s, 4H), 3.40 (br. s, 2H), 2.42 (br. s, 3H), 1.77 (br. s, 2H), 1.60 (d, J=9.79 Hz, 2H). MS cald. for C25H23Cl2FNO3 [(M+H)+] 474, obsd. 474.1.

Workup

  1. customThe solvent was removed
  2. filtrationThe resulting white precipitate was collected by filtration
  3. washwashed with hexanes
  4. customAfter drying in the air
  5. custom62 mg of the crude product was isolated as a white solid
  6. temperaturewith heating
  7. waitThe solution was stored in the freezer for three days
  8. filtrationthe precipitated solids were collected by filtration
  9. washwashed with hexanes
  10. customAfter drying in air

Sources & evidence

ORD record
ord-5421560625a44c4e936839074e4af27e
Source dataset
uspto-grants-2014_04
Patent number
US08691993B2

Reaction notes

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