Sodium Sulfate → N-(4-Bromo-2-(2,2-dimethoxyethyl)phenyl)-8-methyl-8-azabicyclo[3.2.1]octan-3-amine

HRID 1668475

Reaction equation

HRID 1668475 reaction equation
[Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([CH2:9][CH:10]([O:13][CH3:14])[O:11][CH3:12])[CH:3]=1.[CH3:15][N:16]1[CH:21]2[CH2:22][CH2:23][CH:17]1[CH2:18][C:19](=O)[CH2:20]2.S([O-])([O-])(=O)=O.[Na+].[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C.C(OCC)(=O)C>[Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][CH:19]2[CH2:20][CH:21]3[N:16]([CH3:15])[CH:17]([CH2:23][CH2:22]3)[CH2:18]2)=[C:4]([CH2:9][CH:10]([O:13][CH3:14])[O:11][CH3:12])[CH:3]=1

Participants

7

Reactant 4

HCID 24436Sodium SulfateHCID 79038Npc164516HCID 5049666Sodium triacetoxyborohydrideHCID 590046094-Bromo-2-(2,2-dimethoxyethyl)aniline

Product 1

HCID 59004631N-(4-Bromo-2-(2,2-dimethoxyethyl)phenyl)-8-methyl-8-azabicyclo[3.2.1]octan-3-amineYield 36.1%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

Crude compound 67 (225.4 mg, 0.866 mmol) and 8-methyl-8-azabicyclo[3.2.1]octan-3-one (241.1 mg, 1.732 mmol) were stirred in acetic acid (10 mL) under argon in the presence of anhydrous sodium sulfate (1.230 g, 8.660 mmol) at room temperature for 30 minutes. Sodium triacetoxyborohydride (550.6 mg, 2.598 mmol) was then added and the mixture stirred for 24 hours at room temperature. After dilution with a mixture of 8:1 ethyl acetate:Hexanes, the reaction is quenched with saturated sodium bicarbonate. The mixture was transferred to a separatory funnel and the organic layer separated. The organic layer was dried over sodium sulfate and concentrated under reduced pressure and the residue purified via chromatography on silica gel (2M NH3 in methanol:CH2Cl2, 5:95%) to yield a pale yellow residue, 83 (120 mg, 36.1%) as an 5:1 or 1:5 mixture of endo/exo stereoisomers. 1H NMR (major isomer-DMSO-d6) δ 1.56-1.70 (m, 2H), 1.87-1.99 (m, 4H), 2.04-2.09 (m, 2H), 2.21 (s, 3H), 2.79 (d, 2H, J=5.3 Hz), 3.03-3.17 (m, 2H), 3.28 (s, 6H), 3.40-3.49 (m, 1H), 4.54 (t, 1H, J=5.3 Hz), 4.98 (s, 1H), 6.36 (d, 1H, J=9.3 Hz), 7.11-7.21 (m, 2H); ESI-MS (m/z, %): 383/385 (MH+, 100%).

Workup

  1. customHexanes, the reaction is quenched with saturated sodium bicarbonate
  2. customThe mixture was transferred to a separatory funnel
  3. customthe organic layer separated
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customthe residue purified via chromatography on silica gel (2M NH3 in methanol:CH2Cl2, 5:95%)

Sources & evidence

ORD record
ord-71ef11ea241c4131a52ff4f124e724c6
Source dataset
uspto-grants-2011_08
Patent number
US07989447B2

Linked notes

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