Hydrochloric Acid → HCID 11693141, compound

HRID 507133Notes

Reaction equation

HRID 507133 reaction equation
[F:1][C:2]([F:41])([F:40])[C:3]1[CH:4]=[C:5]([CH:33]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:35]=1)[CH2:6][N:7]([C:27]1[N:28]=[N:29][N:30]([CH3:32])[N:31]=1)[C@H:8]1[CH2:14][CH2:13][CH2:12][N:11]([CH2:15][CH2:16][OH:17])[C:10]2[CH:18]=[C:19]([C:23]([F:26])([F:25])[F:24])[C:20]([CH3:22])=[CH:21][C:9]1=2.[H-].[K+].Br[CH2:45][C:46]([OH:48])=[O:47].Cl>O1CCCC1.O.C(OCC)(=O)C>[F:37][C:36]([F:39])([F:38])[C:34]1[CH:33]=[C:5]([CH:4]=[C:3]([C:2]([F:40])([F:1])[F:41])[CH:35]=1)[CH2:6][N:7]([C:27]1[N:28]=[N:29][N:30]([CH3:32])[N:31]=1)[C@H:8]1[CH2:14][CH2:13][CH2:12][N:11]([CH2:15][CH2:16][O:17][CH2:45][C:46]([OH:48])=[O:47])[C:10]2[CH:18]=[C:19]([C:23]([F:24])([F:25])[F:26])[C:20]([CH3:22])=[CH:21][C:9]1=2

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6227Bromoacetic AcidHCID 82127Potassium hydrideHCID 11548876HCID 11548876, compound

Product 1

HCID 11693141HCID 11693141, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-2-{5-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-yl}-ethanol (0.17 mmol) in tetrahydrofuran (5 mL), add potassium hydride (0.67 mmol) at room temperature. After stirring for 30 minutes add bromoacetic acid (0.25 mmol) as a solution in tetrahydrofuran (1 mL). After stirring an additional 0.5 h, quench the reaction with wet tetrahydrofuran (2 mL), dilute with water (1 mL), and ethyl acetate (5 mL). Neutralize the reaction with 5M HCl, separate the organic phase, and wash the aqueous with ethyl acetate (2×5 mL). Dry the combined organic phases over sodium sulfate, filter, and remove solvent under vacuum. Chromatograph the product over silica gel, eluting with methanol/dichloromethane (0.5-4%) to afford the title compound as a colorless foam. MS (ES+): 655 (M+H).

Workup

  1. stirringAfter stirring an additional 0.5 h
  2. customquench
  3. customthe reaction with wet tetrahydrofuran (2 mL)
  4. customseparate the organic phase
  5. washwash the aqueous with ethyl acetate (2×5 mL)
  6. dry with materialDry the combined organic phases over sodium sulfate
  7. filtrationfilter
  8. customremove solvent under vacuum
  9. washChromatograph the product over silica gel, eluting with methanol/dichloromethane (0.5-4%)

Sources & evidence

ORD record
ord-2c87d0de120a4a1f92ddfa44ff44d0b3
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

Loading…