Hydrogen Bromide → HCID 11566769, compound

HRID 747840Notes

Reaction equation

HRID 747840 reaction equation
C([O:4][C:5]1[CH:6]=[C:7]([C:11]23[CH2:20][CH:15]([CH2:16][CH:17]([NH2:19])[CH2:18]2)[N:14]([CH2:21][CH2:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:13][CH:12]3[CH3:30])[CH:8]=[CH:9][CH:10]=1)(C)C.Br.[OH-].[Na+]>C(O)(=O)C>[NH2:19][C@H:17]1[CH2:16][C@H:15]2[CH2:20][C@:11]([C:7]3[CH:6]=[C:5]([OH:4])[CH:10]=[CH:9][CH:8]=3)([C@H:12]([CH3:30])[CH2:13][N:14]2[CH2:21][CH2:22][CH2:23][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH2:18]1

Participants

5

Reactant 3

HCID 260Hydrogen BromideHCID 14798Sodium HydroxideHCID 69216118HCID 69216118, compound

Product 1

HCID 11566769HCID 11566769, compoundYield 98.5%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

7-amino-4-methyl-5-(3-isopropoxyphenyl)-2-(3-phenylpropyl)-2-aza-bicyclo[3.3.1 ]nonane (2.7) (3.07 g, 7.8 mmole) was dissolved in glacial acetic acid (20 mL), 48% HBr (32.5 ml) was added, and the solution was heated to reflux for 15 h. The reaction mixture was allowed to cool to room temperature, poured into ice (100 g), and the pH was raised to 10 with 50% NaOH. The aqueous layer was extracted with 3:1 CH2Cl2:THF (3×100 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated in vacuu. The crude product was purified by flash chromatography using silica gel and eluted with 65:35 CH2Cl2:CMA-80 to yield 2.8 g (88.3%) of the desired product as an off-white solid. The analytical sample was prepared by dissolving the free base in CHCl3, acidifying with HCl in ether, and precipitated with ether. The ether/CHCl3 mixture was decanted and the percipitate taken up in MeOH. The product was then precipitated out of the MeOH with ether. The solvent was decanted and the resultant material was dried under vacuum at 50° C. overnight. [α]D20=−20.5 (c 1.03, MeOH). 1H NMR (CDC13) δ 7.27-7.07 (m, 6H), 6.65-6.58 (m, 3H), 4.33 (br, 2H), 3.54 (br, 1H), 2.79 (m, 1H), 2.66-2.53 (m, 3H), 2.46 (t, J=7.0 Hz, 2H,), 2.31 (m, 3H), 2.04 (br, 1H), 1.77 (t, J=7.2, 2H), 1.53 (m, 1H), 1.14 (m, 1H), 0.98 (m, 1H), 0.70 (d, J=6.9 Hz, 3H,). 13C NMR (CD3OD) δ 159.5, 149.3, 141.9, 131.4, 130.1, 129.9, 127.9, 117.5, 115.1, 114.9, 113.6, 113.4, 89.9, 57.1, 56.2, 55.8, 55.1, 51.4, 46.8, 45.0, 44.1, 40.1, 38.4, 37.4, 34.0, 30.6, 28.4, 27.4, 18.5. Anal. (C24H34Cl2N2O.H2O) C, H, N.

Workup

  1. temperaturethe solution was heated
  2. temperatureto reflux for 15 h
  3. extractionThe aqueous layer was extracted with 3:1 CH2Cl2
  4. dry with materialThe combined organic extracts were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuu
  7. customThe crude product was purified by flash chromatography
  8. washeluted with 65:35 CH2Cl2

Sources & evidence

ORD record
ord-740a103d1fd44eba9fb38e46e5fc5938
Source dataset
uspto-grants-2008_07
Patent number
US07399762B2

Reaction notes

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