Lithium hydroxide, monohydrate → HCID 54583051, compound

HRID 1992055Notes

Reaction equation

HRID 1992055 reaction equation
[CH3:1][C:2]1[N:6]([CH:7]2[CH2:13][CH:12]3[N:14]([CH2:15][CH2:16][C:17]4([C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)[CH2:22][CH2:21][N:20]([C:23]([C:25]5[CH:26]=[C:27]([CH:32]=[CH:33][CH:34]=5)[C:28]([O:30]C)=[O:29])=[O:24])[CH2:19][CH2:18]4)[CH:9]([CH2:10][CH2:11]3)[CH2:8]2)[C:5]2[CH:41]=[CH:42][CH:43]=[CH:44][C:4]=2[N:3]=1.O.[OH-].[Li+].C(=O)(O)[O-].[Na+]>C1COCC1.O>[CH3:1][C:2]1[N:6]([CH:7]2[CH2:13][CH:12]3[N:14]([CH2:15][CH2:16][C:17]4([C:35]5[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=5)[CH2:22][CH2:21][N:20]([C:23]([C:25]5[CH:26]=[C:27]([CH:32]=[CH:33][CH:34]=5)[C:28]([OH:30])=[O:29])=[O:24])[CH2:19][CH2:18]4)[CH:9]([CH2:10][CH2:11]3)[CH2:8]2)[C:5]2[CH:41]=[CH:42][CH:43]=[CH:44][C:4]=2[N:3]=1

Participants

5

Reactant 3

HCID 168937Lithium hydroxide, monohydrateHCID 516892Sodium BicarbonateHCID 54583056HCID 54583056, compound

Product 1

HCID 54583051HCID 54583051, compound

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
0 °C

Procedure

To a precooled (0° C.) stirred solution of methyl 3-[(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidin-1-yl)carbonyl]benzoate 10 (20 mg, 0.034 mmol) in a 2 mL-mixed solvent of THF-H2O (3:1) was added lithium hydroxide monohydrate (4.3 mg, 0.1 mmol). The resulting mixture was stirred for 2 hours at 0° C. before being buffered with saturated sodium bicarbonate solution. The reaction mixture was then extracted with dichloromethane (3×20 mL). The combined extracts were washed with brine and dried over anhydrous sodium sulfate. After evaporation of the solvent, the crude product was purified by flash chromatography on silical gel, eluting with a gradient of 10-30% methanol in ethyl acetate to afford 3-[(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidin-1-yl)carbonyl]benzoic acid 11 as white powder solid (18 mg, 95%). 1H NMR (300 MHz, DMSO-d6) δ 7.98 (s, 1H), 7.91 (s, 1H), 7.51 (d, J=6.9 Hz, 1H), 7.40-7.36 (m, 7H), 7.26-7.24 (m, 2H), 7.14-7.08 (m, 2H), 4.55-4.49 (m, 1H), 3.92 (br, 1H), 3.34 (br, 1H), 4.24 (br, 2H), 2.45 (s, 3H), 2.39-2.32 (m, 3H), 2.14 (br, 3H), 1.86-1.73 (m, 10H), 1.59 (d, J=7.3 Hz, 2H). HRMS m/z (M+H)+ calcd 577.3179; obsd 577.3192.

Workup

  1. extractionThe reaction mixture was then extracted with dichloromethane (3×20 mL)
  2. washThe combined extracts were washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customAfter evaporation of the solvent
  5. customthe crude product was purified by flash chromatography on silical gel
  6. washeluting with a gradient of 10-30% methanol in ethyl acetate

Sources & evidence

ORD record
ord-d7908a6d9e374570bcc2e1f910c25f7a
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

Loading…