Lithium Hydroxide → HCID 67983850, compound

HRID 1748221Notes

Reaction equation

HRID 1748221 reaction equation
[CH:1]1([C:4]2[O:8][N:7]=[C:6]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[O:15][C:16]([F:19])([F:18])[F:17])[C:5]=2[CH2:20][O:21][CH:22]2[CH2:28][CH:27]3[N:29]([C:30]4[CH:42]=[CH:41][C:33]5[C:34]([C:37]([O:39]C)=[O:38])=[N:35][S:36][C:32]=5[CH:31]=4)[CH:24]([CH2:25][CH2:26]3)[CH2:23]2)[CH2:3][CH2:2]1.[Li+].[OH-]>C1COCC1.CO.O>[CH:1]1([C:4]2[O:8][N:7]=[C:6]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[O:15][C:16]([F:17])([F:19])[F:18])[C:5]=2[CH2:20][O:21][CH:22]2[CH2:28][CH:27]3[N:29]([C:30]4[CH:42]=[CH:41][C:33]5[C:34]([C:37]([OH:39])=[O:38])=[N:35][S:36][C:32]=5[CH:31]=4)[CH:24]([CH2:25][CH2:26]3)[CH2:23]2)[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 67983726HCID 67983726, compound

Product 1

HCID 67983850HCID 67983850, compound

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

Methyl 6-(3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)benzo[d]isothiazole-3-carboxylate (37 mg, 0.062 mg) in a 3:2:1 THF-MeOH—H2O solution (1 mL) was treated with a 6N LiOH solution (85 μL, 0.49 mmol) at rt for 12 hours. After this time the organic was removed in vacuo and the residue was diluted with water (1 mL.) and cooled in ice. 3N NaOH was added dropwise until pH 7. The solid that separated was collected by filtration, washed with additional water and dried in vacuo to afford the 6-(3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)benzo[d]isothiazole-3-carboxylic acid as off white solid. 1H NMR (400 MHz, DMSO) δ 8.31 (d, J=8.0 Hz, 1H), 7.68-7.62 (m, 2H), 7.57-7.52 (m, 2H), 7.18 (bs, 1H), 6.90 (d, J=9.2 Hz, 1H), 4.31 (s, 2H), 4.18 (bs, 2H), 3.42 (m, 1H), 1.88-1.84 (m, 2H), 1.80 (1.78 (m, 4H), 1.53-1.49 (m, 2H), 1.15-1.03 (m, 5H). MS m/z 586.2 (M+1).

Workup

  1. customAfter this time the organic was removed in vacuo
  2. additionthe residue was diluted with water (1 mL.)
  3. temperaturecooled in ice
  4. addition3N NaOH was added dropwise until pH 7
  5. customThe solid that separated
  6. filtrationwas collected by filtration
  7. washwashed with additional water
  8. customdried in vacuo

Sources & evidence

ORD record
ord-bc2b47419b6642e6a62b233b6164f2c0
Source dataset
uspto-grants-2015_10
Patent number
US09150568B2

Reaction notes

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