Tri-o-tolylphosphine → Ammonia

HRID 1433288Notes

Reaction equation

HRID 1433288 reaction equation
[C:1]([O:5][C:6](=[O:22])[NH:7][CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH2:18][CH2:19][CH:20]=[CH2:21])=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].[CH2:23]([O:30][C:31]1[CH:36]=[CH:35][C:34](Br)=[CH:33][C:32]=1[C@@H:38]([C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)[CH2:39][CH2:40][N:41]([CH:45]([CH3:47])[CH3:46])[CH:42]([CH3:44])[CH3:43])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(C(C)C)CC)(C)C>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH3:7].[C:1]([O:5][C:6](=[O:22])[NH:7][CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH2:18][CH2:19]/[CH:20]=[CH:21]/[C:34]2[CH:35]=[CH:36][C:31]([O:30][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[C:32]([C@@H:38]([C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)[CH2:39][CH2:40][N:41]([CH:42]([CH3:44])[CH3:43])[CH:45]([CH3:46])[CH3:47])[CH:33]=2)=[CH:12][CH:11]=1)([CH3:3])([CH3:2])[CH3:4]

Participants

8

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 24885301(R)-3-(2-benzyloxy)-5-bromophenyl)-N,N-diisopropyl-3-phenylpropan-1-amineHCID 57933209Tert-butyl{2-[4-(pent-4-en-1-yloxy)phenyl]ethyl}carbamate

Product 2

HCID 222AmmoniaHCID 57933225tert-butyl[2-(4-{[(4E)-5-{4-(benzyloxy)-3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenyl}pent-4-en-1-yl]oxy}phenyl)ethyl]carbamate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

tert-butyl{2-[4-(pent-4-en-1-yloxy)phenyl]ethyl}carbamate (Preparation 56, 1.2 g, 3.9 mmol), (3R)-3-[2-(benzyloxy)-5-bromophenyl]-N,N-diisopropyl-3-phenylpropan-1-amine (Prepared according to WO9411337, 1.9 g, 3.9 mmol), palladium acetate (90 mg, 0.4 mmol), tri(o-tolyl)phosphine (200 mg, 0.8 mmol), and diisopropylethylamine (1.0 ml, 5.9 mmol) were mixed in acetonitrile (12 ml), degassed with argon and the heated to 90° C. for 5 hours. The reaction was cooled to room temperature, filtered through Arbocel and solvent removed in vacuo. The residue was taken up in water and ethyl acetate, the organics were separated, 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 (981210.2 to 95151.5 by volume) to furnish the title compound as a pale yellow foam, 2.5 g.

Workup

  1. customdegassed with argon
  2. temperatureThe reaction was cooled to room temperature
  3. filtrationfiltered through Arbocel and solvent
  4. customremoved in vacuo
  5. customethyl acetate, the organics were separated
  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-2582f6eca6a0447492ea662a2073caf8
Source dataset
uspto-grants-2009_11
Patent number
US07612084B2

Reaction notes

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