Potassium Iodide → Ammonia

HRID 1433268Notes

Reaction equation

HRID 1433268 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C@@H:23]([O:26][Si:27]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28])[CH2:24]Br)[CH:12]=[C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.Cl.[NH2:36][CH2:37][CH2:38][C:39]1[CH:72]=[CH:71][C:42]([O:43][CH2:44][CH2:45][CH2:46][CH2:47][C:48]2[CH:53]=[CH:52][C:51]([OH:54])=[C:50]([C@@H:55]([C:65]3[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=3)[CH2:56][CH2:57][N:58]([CH:62]([CH3:64])[CH3:63])[CH:59]([CH3:61])[CH3:60])[CH:49]=2)=[CH:41][CH:40]=1.C(=O)([O-])O.[Na+].[I-].[K+].C(#N)CC>C(OCC)(=O)C>[NH3:36].[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C@@H:23]([O:26][Si:27]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28])[CH2:24][NH:36][CH2:37][CH2:38][C:39]2[CH:40]=[CH:41][C:42]([O:43][CH2:44][CH2:45][CH2:46][CH2:47][C:48]3[CH:53]=[CH:52][C:51]([OH:54])=[C:50]([C@@H:55]([C:65]4[CH:66]=[CH:67][CH:68]=[CH:69][CH:70]=4)[CH2:56][CH2:57][N:58]([CH:59]([CH3:60])[CH3:61])[CH:62]([CH3:64])[CH3:63])[CH:49]=3)=[CH:71][CH:72]=2)[CH:12]=[C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 4875Potassium IodideHCID 7854PropionitrileHCID 516892Sodium Bicarbonate2×HCID 57683377{(1R)-1-[3,5-bis(benzyloxy)phenyl]-2-bromoethoxy}(tert-butyl)dimethylsilaneHCID 866164804-{4-[4-(2-Aminoethyl)phenoxy]butyl}-2-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenol bis hydrochloride salt

Product 2

HCID 222AmmoniaHCID 579332204-(4-[4-(2-{[(2R)-2-[3,5-bis(benzyloxy)phenyl]-2-{[tert-butyl(dimethyl)silyl]oxy}ethyl]amino}ethyl)phenoxy]butyl}-2-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenol

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

{(1R)-1-[3,5-bis(benzyloxy)phenyl]-2-bromoethoxy}(tert-butyl)dimethylsilane (Prepared according to US2005/222128, 570 mg, 1.1 mmol), 4-{4-[4-(2-aminoethyl)phenoxy]butyl}-2-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenol bis hydrochloride salt (Preparation 13, 746 mg, 1.3 mmol), sodium hydrogen carbonate (544 mg, 6.48 mmol) and potassium iodide (50 mg, 0.30 mmol) were added to propionitrile (8 ml) and heated to 90° C. and left to stir overnight. After cooling, ethyl acetate and saturated aqueous sodium hydrogen carbonate were added, organics separated and washed with more saturated aqueous sodium hydrogen carbonate, then brine and then dried (magnesium sulphate) and solvent removed in vacuo. The residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol:880 ammonia (100:0:0 to 94:6:0.6 by volume) to furnish the title compound as a yellow oil, 720 mg.

Workup

  1. waitleft
  2. temperatureAfter cooling
  3. customorganics separated
  4. washwashed with more saturated aqueous sodium hydrogen carbonate
  5. dry with materialbrine and then dried (magnesium sulphate) and solvent
  6. customremoved in vacuo
  7. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane

Sources & evidence

ORD record
ord-f9012b7bcd2f4f87a7b7ed99acfa2ddb
Source dataset
uspto-grants-2009_11
Patent number
US07612084B2

Reaction notes

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