Water → Ammonia

HRID 1433252Notes

Reaction equation

HRID 1433252 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[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.[C:32](=[O:35])([O-:34])[O-].[Cs+].[Cs+].[C:38]([O:42][C:43](=[O:53])[NH:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51]Br)([CH3:41])([CH3:40])[CH3:39].O>CN(C)C=O.[Cl-].[Na+].O>[NH3:19].[C:2]([O:34][C:32]([N:44]([CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][O:15][C:12]1[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[C:10]([C@@H:16]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH2:17][CH2:18][N:19]([CH:20]([CH3:22])[CH3:21])[CH:23]([CH3:24])[CH3:25])[CH:11]=1)[C:43]([O:42][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:53])=[O:35])([CH3:7])([CH3:3])[CH3:1]

Participants

8

Reactant 4

HCID 962WaterHCID 10796Cesium carbonate3×HCID 10108474tert-butyl N-(7-bromoheptyl)carbamate3×HCID 579331854-(Benzyloxy)-3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenol

Product 2

HCID 222AmmoniaHCID 69008693Di-tert-butyl(7-{4-(benzyloxy)-3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenoxy}heptyl)imidodicarbonate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

4-(Benzyloxy)-3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenol (Preparation 16, 150 mg, 0.36 mmol) was dissolved in dimethylformamide (2 ml), caesium carbonate (140 mg, 0.43 mmol) was added and stirred at room temperature for 30 minutes. tert-Butyl(7-bromoheptyl)carbamate (Prepared according to J. Med. Chem., 1994, 137, p2537-2551; 170 mg, 0.43 mmol), dissolved in dimethylformamide (1 ml), was added and heated to 70oC. After 2.5 hours caesium carbonate (70 mg, 0.22 mmol) was added and after a further 10 minutes tert-butyl(7-bromoheptyl)carbamate (70 mg, 0.18 mmol) was added. After 1 hour caesium carbonate (20 mg, 0.06 mmol) and tert-butyl(7-bromoheptyl)carbamate (35 mg, 0.09 mmol) were added and after 1 hour at 70° C. the mixture was cooled to room temperature and stirred for 3 days before the addition of water and brine were added, the mixture extracted with ethyl acetate, 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 (98/2/0.2 to 95/5/0.5 by volume) to furnish the title compound as a colourless gum, 220 mg.

Workup

  1. additionwas added
  2. temperatureheated to 70oC
  3. additionwas added
  4. temperaturewas cooled to room temperature
  5. additionwere added
  6. extractionthe mixture extracted with ethyl acetate
  7. dry with materialdried (magnesium sulphate)
  8. filtrationfiltered
  9. customthe solvents removed in vacuo
  10. customthe residue was purified by column chromatography on silica gel eluting with dichloromethane

Sources & evidence

ORD record
ord-34bb0e0b25ff42a18a2d6a8be1db03ff
Source dataset
uspto-grants-2009_11
Patent number
US07612084B2

Reaction notes

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