Hydrochloric Acid → (4-{5-[(3,5-Bis-trifluoromethyl-benzyl)-(3-methyl-isoxazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-ylmethyl}-cyclohexyl)-acetic acid

HRID 507117Notes

Reaction equation

HRID 507117 reaction equation
[OH-].[Na+].C[O:4][C:5](=[O:52])[CH2:6][CH:7]1[CH2:12][CH2:11][CH:10]([CH2:13][N:14]2[CH2:20][CH2:19][CH2:18][CH:17]([N:21]([CH2:28][C:29]3[CH:34]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:32]=[C:31]([C:39]([F:42])([F:41])[F:40])[CH:30]=3)[C:22]3[O:26][N:25]=[C:24]([CH3:27])[CH:23]=3)[C:16]3[CH:43]=[C:44]([CH3:51])[C:45]([C:47]([F:50])([F:49])[F:48])=[CH:46][C:15]2=3)[CH2:9][CH2:8]1.Cl>CO>[F:42][C:39]([F:40])([F:41])[C:31]1[CH:30]=[C:29]([CH:34]=[C:33]([C:35]([F:36])([F:38])[F:37])[CH:32]=1)[CH2:28][N:21]([C:22]1[O:26][N:25]=[C:24]([CH3:27])[CH:23]=1)[CH:17]1[CH2:18][CH2:19][CH2:20][N:14]([CH2:13][CH:10]2[CH2:9][CH2:8][CH:7]([CH2:6][C:5]([OH:52])=[O:4])[CH2:12][CH2:11]2)[C:15]2[CH:46]=[C:45]([C:47]([F:49])([F:48])[F:50])[C:44]([CH3:51])=[CH:43][C:16]1=2

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 11664840(4-(5-[(3,5-Bis-trifluoromethyl-benzyl)-(3-methyl-isoxazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-ylmethyl}-cyclohexyl)-acetic acid methyl ester

Product 1

HCID 11686270(4-{5-[(3,5-Bis-trifluoromethyl-benzyl)-(3-methyl-isoxazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-ylmethyl}-cyclohexyl)-acetic acidYield 95%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

Add 5 N sodium hydroxide solution (2 mL) to a solution of (4-{5-[(3,5-bis-trifluoromethyl-benzyl)-(3-methyl-isoxazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-ylmethyl}-cyclohexyl)-acetic acid methyl ester (63 mg, 0.088 mmol) in methanol (5 mL) and heat at 60° C. for 4 h. After the reaction cools to room temperature, acidify to pH 4 with 2 N hydrochloric acid solution and extract the aqueous mixture with ethyl acetate (3×10 mL). Wash the organic layer with water and brine (10 mL each). Dry the organic layer over anhydrous sodium sulfate, filter and remove the solvent under reduced pressure to provide the title compound as an off-white solid (58 mg, 95%). 1H NMR (CDCl3, 300 MHz) δ 0.78-2.45 (m, 22H), 2.63-3.10 (m, 4H), 4.61-4.82 (m, 3H), 5.12-5.19 (m, 1H), 6.89 (s, 1H), 7.12-7.33 (m, 2H), 7.62-7.81 (m, 3H); ESI MS m/z 706 [C34H36F9N3O3+H]+; HPLC 96.3%, tR 18.9 min.

Workup

  1. customcools to room temperature
  2. extractionextract the aqueous mixture with ethyl acetate (3×10 mL)
  3. washWash the organic layer with water and brine (10 mL each)
  4. dry with materialDry the organic layer over anhydrous sodium sulfate
  5. filtrationfilter
  6. customremove the solvent under reduced pressure

Sources & evidence

ORD record
ord-fda91d91c5e74648b678bc9c306d7f66
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

Loading…