1,2-Dibromoethane → (R)-N,N-Diisopropyl-3-(5-azido-2-benzyloxyphenyl)-3-phenylpropanamine

HRID 428326

Reaction equation

HRID 428326 reaction equation
[CH:1]([N:4]([CH:29]([CH3:31])[CH3:30])[CH2:5][CH2:6][C@@H:7]([C:14]1[CH:19]=[C:18](Br)[CH:17]=[CH:16][C:15]=1[O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([CH3:3])[CH3:2].BrCCBr.S([N:46]=[N+:47]=[N-:48])(C1C=CC(C)=CC=1)(=O)=O.O.O.O.O.O.O.O.O.O.O.[O-]P(OP([O-])([O-])=O)(=O)[O-].[Na+].[Na+].[Na+].[Na+].[K+].[Br-]>C1COCC1.C(OCC)C.O>[CH:1]([N:4]([CH:29]([CH3:31])[CH3:30])[CH2:5][CH2:6][C@@H:7]([C:14]1[CH:19]=[C:18]([N:46]=[N+:47]=[N-:48])[CH:17]=[CH:16][C:15]=1[O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([CH3:3])[CH3:2]

Participants

9

Reactant 5

HCID 78391,2-DibromoethaneHCID 13661p-Toluenesulfonyl azideHCID 253877Potassium BromideHCID 3084150Sodium pyrophosphate decahydrateHCID 24885301(R)-3-(2-benzyloxy)-5-bromophenyl)-N,N-diisopropyl-3-phenylpropan-1-amine

Product 1

HCID 54067329(R)-N,N-Diisopropyl-3-(5-azido-2-benzyloxyphenyl)-3-phenylpropanamine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of (R)-N,N-diisopropyl-3-(2-benzyloxy-5-bromophenyl)-3-phenylpropanamine (10.00 g, 20.81 mmol) (prepared as described in WO 94/11337, Example 1) and Mg (1.57 g, 64.52 mmol) in THF (50 mL) was added 1,2-dibromoethane (3.59 mL, 41.63 mmol) and the solution was self-refluxing for a while. The mixture was refluxed for 1 h whereafter the solution was cooled and tosyl azide (4.10 g, 20.81 mmol) in diethyl ether (100 mL) was added with constant stirring while keeping the temperature at 0° C. wherafter the temperature was allowed to rise to room temperature for 4 h. A solution of tetra-sodium pyrophosphate decahydrate (4.46 g, 10.00 mmol) in 50 mL water was added. A precipitate was filtered off and the filtrate was evaporated. The residue was extracted with diethyl ether, the organic phase was dried (MgSO4) and evaporated. The residue was chromatographed on silica (n-hexane-ethanol, 8:2). The product was crystallised from ethanol to give 1.15 g (13%); IR (KBr) 2116 (N3) cm−1; 1H NMR (CDCl3) δ0.92 (d, 12H), 2.10 (m, 2H), 2.33 (m, 2H), 2.95 (m, 2H), 4.40 (t, 1H), 5.00 (s, 2H), 6.81 (d, 2H), 6.97 (s, 1H), 7.10-7.40 (m, 10H).

Workup

  1. temperaturethe solution was self-refluxing for a while
  2. temperatureThe mixture was refluxed for 1 h whereafter the solution
  3. temperaturewas cooled
  4. customat 0° C.
  5. filtrationA precipitate was filtered off
  6. customthe filtrate was evaporated
  7. extractionThe residue was extracted with diethyl ether
  8. dry with materialthe organic phase was dried (MgSO4)
  9. customevaporated
  10. customThe residue was chromatographed on silica (n-hexane-ethanol, 8:2)
  11. customThe product was crystallised from ethanol
  12. customto give 1.15 g (13%)

Sources & evidence

ORD record
ord-50a7a5709c8a4207a52d2e4865a61e26
Source dataset
uspto-grants-2001_11
Patent number
US06313132B1

Linked notes

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