Lithium hydroxide, monohydrate → HCID 71603264, compound

HRID 2363882Notes

Reaction equation

HRID 2363882 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[C:28]([Cl:29])=[CH:27][CH:26]=[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>[Cl:30][C:24]1[CH:25]=[CH:26][CH:27]=[C:28]([Cl:29])[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

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86686921HCID 86686921, compound

Product 1

HCID 71603264HCID 71603264, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of {4-[1-(2,6-dichloro-benzoyl)-piperidin-4-yl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid methyl ester (96 mg, 0.197 mmol) in THF (8.0 mL) was added a solution of lithium hydroxide monohydrate (94.2 mg, 2.2 mmol) in water (2 mL). The reaction mixture was stirred at room temperature overnight. After this time, the reaction mixture was concentrated. Water (˜20 mL) was added and the mixture was acidified with 1.0 N aqueous HCl (3.9 mL). The resulting white precipitate was collected by vacuum filtration, washed with hexanes, and then further dried under vacuum to {4-[1-(2,6-dichloro-benzoyl)-piperidin-4-yl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid (66 mg, 71%). 1H NMR (300 MHz, DMSO-d6) δ ppm 7.84-7.97 (m, 2H), 7.68 (s, 1H), 7.55-7.66 (m, 2H), 7.44-7.53 (m, 1H), 7.34 (s, 1H), 4.69-4.80 (m, 1H), 3.76 (br. s., 2H), 3.32 (br. s., 6H), 2.43 (s, 2H), 1.57-1.85 (m, 2H). MS cald. for C25H23Cl2FNO3 [(M+H)+]: 474, obsd. 474.1.

Workup

  1. concentrationAfter this time, the reaction mixture was concentrated
  2. additionWater (˜20 mL) was added
  3. filtrationThe resulting white precipitate was collected by vacuum filtration
  4. washwashed with hexanes
  5. dry with materialfurther dried under vacuum to {4-[1-(2,6-dichloro-benzoyl)-piperidin-4-yl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid (66 mg, 71%)

Sources & evidence

ORD record
ord-92b5daac82484503a6001401443cb34e
Source dataset
uspto-grants-2014_04
Patent number
US08691993B2

Reaction notes

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