Tri-o-tolylphosphine → Ammonia

HRID 1433284Notes

Reaction equation

HRID 1433284 reaction equation
[CH2:1]([N:9]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH:7]=[CH2:8].[CH2:24]([O:31][C:32]1[CH:37]=[CH:36][C:35](Br)=[CH:34][C:33]=1[C@@H:39]([C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)[CH2:40][CH2:41][N:42]([CH:46]([CH3:48])[CH3:47])[CH:43]([CH3:45])[CH3:44])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)C(C)C)(C)C.C(=O)([O-])O.[Na+]>C([O-])(=O)C.C([O-])(=O)C.[Pd+2].C(OCC)(=O)C.C(#N)C>[NH3:9].[C:13]([O:12][C:10]([N:9]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]/[CH:7]=[CH:8]/[C:35]1[CH:36]=[CH:37][C:32]([O:31][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[C:33]([C@@H:39]([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[CH2:40][CH2:41][N:42]([CH:43]([CH3:45])[CH3:44])[CH:46]([CH3:47])[CH3:48])[CH:34]=1)[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[O:11])([CH3:14])([CH3:15])[CH3:16]

Participants

10

Reactant 5

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 24885301(R)-3-(2-benzyloxy)-5-bromophenyl)-N,N-diisopropyl-3-phenylpropan-1-amineHCID 57933160Di-tert-butyl oct-7-en-1-ylimidodicarbonate

Product 2

HCID 222AmmoniaHCID 57933221di-tert-butyl[(7E)-8-{4-(benzyloxy)-3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenyl}oct-7-en-1-yl]imidodicarbonate

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

di-tert-butyl oct-7-en-1-ylimidodicarbonate (Preparation 48, 649 mg, 1.98 mmol), (3R)-3-[2-(benzyloxy)-5-bromophenyl]-N,N-diisopropyl-3-phenylpropan-1-amine (Prepared according to WO1994/11337, 560 mg, 1.16 mmol), palladium diacetate (27 mg, 0.12 mmol), tris(2-methylphenyl)phosphine (73 mg, 0.24 mmol) and N,N-diisopropylethylamine (0.304 ml, 1.75 mmol) were added to acetonitrile (6 ml) and the mixture was heated to 90° C. and left to stir overnight under nitrogen. Mixture was cooled and saturated aqueous sodium hydrogen carbonate and ethyl acetate were added. Organics separated and washed with saturated aqueous sodium hydrogen carbonate, brine, 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 (100/0/0 to 96/4/0.4 by volume) to furnish the title compound as a oil, 530 mg.

Workup

  1. waitleft
  2. temperatureMixture was cooled
  3. customOrganics separated
  4. washwashed with saturated aqueous sodium hydrogen carbonate, brine
  5. dry with materialdried (magnesium sulphate)
  6. customthe solvent removed in vacuo
  7. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane

Sources & evidence

ORD record
ord-6f12f1367def4b99b30b7f65ad290513
Source dataset
uspto-grants-2009_11
Patent number
US07612084B2

Reaction notes

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