Tri-o-tolylphosphine → Ammonia

HRID 1433259Notes

Reaction equation

HRID 1433259 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12](Br)=[CH:11][C:10]=1[C@@H:16]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[CH2:17][CH2:18][N:19]([CH:23]([CH3:25])[CH3:24])[CH:20]([CH3:22])[CH3:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:32]([O:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][C:42]#[N:43])[CH2:33][CH:34]=[CH2:35].C(N(C(C)C)CC)(C)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH3:19].[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12](/[CH:35]=[CH:34]/[CH2:33][CH2:32][O:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][C:42]#[N:43])=[CH:11][C:10]=1[C@@H:16]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[CH2:17][CH2:18][N:19]([CH:23]([CH3:25])[CH3:24])[CH:20]([CH3:22])[CH3:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 24885301(R)-3-(2-benzyloxy)-5-bromophenyl)-N,N-diisopropyl-3-phenylpropan-1-amineHCID 579331896-(But-3-en-1-yloxy)hexanenitrile

Product 2

HCID 222AmmoniaHCID 57933174HCID 57933174, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

(3R)-3-[2-(Benzyloxy)-5-bromophenyl]-N,N-diisopropyl-3-phenylpropan-1-amine (WO9411337, 1.21 g, 2.50 mmol) was dissolved in acetonitrile (8 ml) and 6-(but-3-en-1-yloxy)hexanenitrile (Preparation 23, 708 mg, 4.20 mmol), diisopropylethylamine (0.64 ml, 3.75 mmol), palladium acetate (54 mg, 0.25 mmol) and tri(o-tolyl)phosphine (145 mg, 0.25 mmol) were added. The stirred reaction was heated at 90° C., under a nitrogen atmosphere, for 12 hours, cooled to room temperature and the solvent removed in vacuo. The residue was dissolved in ethyl acetate (50 ml) and washed with saturated aqueous sodium hydrogen carbonate (50 ml), brine (50 ml), dried (magnesium sulphate) and the solvent removed in vacuo. The residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol:880 ammonia (95/5/0.5 by volume) to furnish the title compound as an oil, 960 mg.

Workup

  1. customThe stirred reaction
  2. temperaturecooled to room temperature
  3. customthe solvent removed in vacuo
  4. dissolutionThe residue was dissolved in ethyl acetate (50 ml)
  5. washwashed with saturated aqueous sodium hydrogen carbonate (50 ml), brine (50 ml)
  6. dry with materialdried (magnesium sulphate)
  7. customthe solvent removed in vacuo
  8. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane

Sources & evidence

ORD record
ord-98d7851093274cb3a6c420dee092ffe9
Source dataset
uspto-grants-2009_11
Patent number
US07612084B2

Reaction notes

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