Hydrochloric Acid → Ammonia

HRID 1433256Notes

Reaction equation

HRID 1433256 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][OH:17])=[CH:11][C:10]=1[C@@H:18]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:19][CH2:20][N:21]([CH:25]([CH3:27])[CH3:26])[CH:22]([CH3:24])[CH3:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(/C(OC(C)(C)C)=O)=N\C(OC(C)(C)C)=O.C(OC(=O)[NH:75][CH2:76][CH2:77][C:78]1[CH:83]=[CH:82][C:81](O)=[CH:80][CH:79]=1)(C)(C)C.Cl>O1CCCC1>[NH3:21].[NH2:75][CH2:76][CH2:77][C:78]1[CH:83]=[CH:82][C:81]([O:17][CH2:16][CH2:15][C:12]2[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[C:10]([C@@H:18]([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[CH2:19][CH2:20][N:21]([CH:25]([CH3:26])[CH3:27])[CH:22]([CH3:23])[CH3:24])[CH:11]=2)=[CH:80][CH:79]=1

Participants

8

Reactant 5

HCID 313Hydrochloric Acid2×HCID 11776TriphenylphosphineHCID 6034084Di-tert-butyl diazene-1,2-dicarboxylateHCID 11831452tert-butyl N-(2-(4-hydroxyphenyl)ethyl)carbamateHCID 537612552-{4-(benzyloxy)-3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenyl}ethanol

Product 2

HCID 222AmmoniaHCID 57933208(3R)-3-[5-{2-[4-(2-aminoethyl)phenoxy]ethyl}-2-(benzyloxy)phenyl]-N,N-diisopropyl-3-phenylpropan-1-amine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-{4-(benzyloxy)-3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenyl}ethanol (Prepared according to WO9843942, 390 mg, 0.88 mmol) was dissolved in tetrahydrofuran (6 ml), triphenylphosphine (344 mg, 1.31 mmol) then di-tert-butyl(E)-diazene-1,2-dicarboxylate (265 mg, 1.31 mmol) was added and the mixture was stirred for 20 minutes. tert-butyl[2-(4-hydroxyphenyl)ethyl]carbamate (Prepared according to WO2004/020415, 311 mg, 1.31 mmol) was then added and the reaction was stirred over night. Hydrogen chloride (4M in diethyl ether, ml) was added and left to stir for 3 days, then hydrochloric acid (2M, 5 ml) was added and after 1 hour the mixture was washed with diethyl ether, basified with 2N sodium hydroxide, extracte with diethyl ether, dried (magnesium sulphate), filtered and the solvents removed in vacuo and the residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol:880 ammonia (242/8/0.8 to 95/5/0.5 by volume) to furnish the title compound as a colourless oil, 100 mg.

Workup

  1. stirringthe reaction was stirred over night
  2. waitleft
  3. stirringto stir for 3 days
  4. washwas washed with diethyl ether
  5. dry with materialdried (magnesium sulphate)
  6. filtrationfiltered
  7. customthe solvents removed in vacuo
  8. customthe residue was purified by column chromatography on silica gel eluting with dichloromethane

Sources & evidence

ORD record
ord-2cc5c67f2d4d40169f0c01cc3b0c53cc
Source dataset
uspto-grants-2009_11
Patent number
US07612084B2

Reaction notes

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