Hydrochloric Acid → HCID 70010103, compound

HRID 1267907Notes

Reaction equation

HRID 1267907 reaction equation
Br[CH2:2][C@@H:3]1[CH2:9][C@:8]2([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[NH:10][C@H:4]1[CH2:5][CH2:6][C@H:7]2[NH:17][CH2:18][C:19]1[CH:24]=[C:23]([O:25][C:26]([F:29])([F:28])[F:27])[CH:22]=[CH:21][C:20]=1[O:30][CH:31]1[CH2:33][CH2:32]1.[Na].[CH3:35][S:36]([OH:38])=[O:37].[ClH:39]>CN(C)C=O.C(OCC)(=O)C.O>[ClH:39].[ClH:39].[CH:31]1([O:30][C:20]2[CH:21]=[CH:22][C:23]([O:25][C:26]([F:29])([F:27])[F:28])=[CH:24][C:19]=2[CH2:18][NH:17][C@@H:7]2[CH2:6][CH2:5][C@@H:4]3[NH:10][C@@:8]2([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:9][C@H:3]3[CH2:2][S:36]([CH3:35])(=[O:38])=[O:37])[CH2:32][CH2:33]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 87251Methanesulfinic acidHCID 5360545SodiumHCID 10229986HCID 10229986, compound

Product 1

HCID 70010103HCID 70010103, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

(1R*,2R*,5S*,6R*)-6-(Bromomethyl)-2-(2-cyclopropoxy-5-(trifluoromethoxy)benzylamino)-1-phenyl-8-azabicyclo[13.2.1]octane (Example 20; 200 mg, 0.38 mmol) was dissolved in N,N-dimethylformamide (5 mL) and the solution treated with the sodium salt of methanesulfinic acid (388 mg, 3.8 mmol). The resulting suspension was heated at 110° C. for 1 hour, then cooled and poured into water (50 mL). The mixture was extracted with ethyl acetate (2×20 mL), the extracts were dried (MgSO4) and then concentrated to give a gum. This was purified by silica chromatography to give the pure free base, which was dissolved in ethyl acetate (10 mL). Ethereal hydrogen chloride (2 mL, 1M) solution was added and the solid formed was removed by filtration and recrystallized from methanol/diethyl ether to give the title compound as a white powder (120 mg, 0.20 mmol).

Workup

  1. temperaturecooled
  2. extractionThe mixture was extracted with ethyl acetate (2×20 mL)
  3. dry with materialthe extracts were dried (MgSO4)
  4. concentrationconcentrated
  5. customto give a gum
  6. customThis was purified by silica chromatography
  7. customto give the pure free base, which
  8. customthe solid formed
  9. customwas removed by filtration
  10. customrecrystallized from methanol/diethyl ether

Sources & evidence

ORD record
ord-c652832d3e6c4b49958e606eae4fd746
Source dataset
uspto-grants-2003_04
Patent number
US06555552B2

Reaction notes

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