Lithium hydroxide, monohydrate → HCID 71604176, compound

HRID 2363867Notes

Reaction equation

HRID 2363867 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][CH:29]=[C:28]([Cl:32])[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:28]1[CH:27]=[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:24])=[O:23])[CH:31]=[CH:30][CH:29]=1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86686913HCID 86686913, compound

Product 1

HCID 71604176HCID 71604176, compoundYield 18%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution {4-[1-(3-chloro-phenylmethanesulfonyl)-piperidin-4-yl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid methyl ester (52.4 mg, 0.104 mmol) in THF (8.0 mL) was added a solution of lithium hydroxide monohydrate (49.8 mg, 2.08 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 (2.1 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-(3-chloro-phenylmethanesulfonyl)-piperidin-4-yl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid (9 mg, 18%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.44 (br. s, 1H), 7.95-8.12 (m, 1H), 7.90 (dd, J=9.03, 6.53 Hz, 1H), 7.65-7.74 (m, 2H), 7.55 (s, 1H), 7.46 (d, J=1.00 Hz, 2H), 7.36 (t, J=9.00 Hz, 1H), 4.54 (br. s., 2H), 4.13 (dd, J=5.52, 3.51 Hz, 1H), 3.78 (br. s., 4H), 3.48-3.65 (m, 1H), 2.91-3.22 (m, 3H), 2.42 (br. s., 5H), 1.69 (m, 2H). MS cald. for C25H26ClFNO4S [(M+H)+]: 490, obsd. 490.2.

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-86778be45bd348c6953180b5b3285900
Source dataset
uspto-grants-2014_04
Patent number
US08691993B2

Reaction notes

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