Lithium hydroxide, monohydrate → HCID 71604236, compound

HRID 2363869Notes

Reaction equation

HRID 2363869 reaction equation
C[O:2][C:3](=[O:34])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([CH:16]2[CH2:21][CH2:20][N:19]([S:22]([CH2:25][C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=3)(=[O:24])=[O:23])[CH2:18][CH2:17]2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:33])[CH:11]=2)[CH:6]=1.O.[OH-].[Li+]>C1COCC1.O>[Cl:32][C:29]1[CH:30]=[CH:31][C:26]([CH2:25][S:22]([N:19]2[CH2:20][CH2:21][CH:16]([C:13]3[C:12]4[C:7](=[CH:8][CH:9]=[C:10]([F:33])[CH:11]=4)[CH:6]=[C:5]([CH2:4][C:3]([OH:34])=[O:2])[C:14]=3[CH3:15])[CH2:17][CH2:18]2)(=[O:23])=[O:24])=[CH:27][CH:28]=1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86686914HCID 86686914, compound

Product 1

HCID 71604236HCID 71604236, compoundYield 40.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution {4-[1-(4-chloro-phenylmethanesulfonyl)-piperidin-4-yl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid methyl ester (28.5 mg, 0.057 mmol) in THF (8.0 mL) was added a solution of lithium hydroxide monohydrate (27.3 mg, 1.14 mmol) in water (2.0 mL) at room temperature. The resulting solution was stirred overnight under a nitrogen atmosphere. The solvent was evaporated. Water (˜25 mL) was added and the mixture was acidified with 1.0 N aqueous HCl (1.1 mL). The resulting white precipitate was collected by filtration, washed with water and hexanes, and dried under high vacuum. This crude product was further purified using preparative reverse-phase HPLC to give {4-[1-(4-chloro-phenylmethanesulfonyl)-piperidin-4-yl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid (11.2 mg, 40%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.42 (br. s, 1H), 7.90 (dd, J=9.00, 6.50 Hz, 1H), 7.78-8.11 (m, 1H), 7.69 (s, 1H), 7.50 (s, 4H), 7.36 (td, J=9.00, 2.50 Hz, 1H), 4.53 (br. s, 2H), 3.64-3.86 (m, 5H), 2.91-3.19 (m, 3H), 2.41 (br. s., 3H), 2.15-2.35 (br. s, 1H), 1.61-1.73 (m, 2H). MS cald. for C25H25ClFNO4S [(M+H)+]: 490, obsd. 490.1.

Workup

  1. customThe solvent was evaporated
  2. additionWater (˜25 mL) was added
  3. filtrationThe resulting white precipitate was collected by filtration
  4. washwashed with water and hexanes
  5. customdried under high vacuum
  6. customThis crude product was further purified

Sources & evidence

ORD record
ord-885b3f9f18e24479993102926507d3c2
Source dataset
uspto-grants-2014_04
Patent number
US08691993B2

Reaction notes

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