Hydrogen Bromide → Lasofoxifene

HRID 1822615Notes

Reaction equation

HRID 1822615 reaction equation
C[O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C@@H:9]([C:13]1[CH:26]=[CH:25][C:16]([O:17][CH2:18][CH2:19][N:20]3[CH2:24][CH2:23][CH2:22][CH2:21]3)=[CH:15][CH:14]=1)[C@@H:8]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH2:7][CH2:6]2.Br>C(O)(=O)C>[C:27]1([C@H:8]2[CH2:7][CH2:6][C:5]3[CH:4]=[C:3]([OH:2])[CH:12]=[CH:11][C:10]=3[C@H:9]2[C:13]2[CH:26]=[CH:25][C:16]([O:17][CH2:18][CH2:19][N:20]3[CH2:24][CH2:23][CH2:22][CH2:21]3)=[CH:15][CH:14]=2)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

4

Reactant 2

HCID 260Hydrogen BromideHCID 11373717rac 7-Methoxy Lasofoxifene

Product 1

HCID 216416Lasofoxifene

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of cis-1-[2-[4-(6-methoxy-2-phenyl-1,2,3,4 tetrahydronaphthalen-1-yl)phenoxy] ethyl}pyrrolidine (12 g, 28 mmol), acetic acid (75 mL), and 48% HBr (75 mL) was heated at 100° C. for 15 h. The solution was cooled and the resulting white precipitate was collected by filtration. The hydrobromide salt (9.6 g, 69%) was dissolved in CHCl3/MeOH and was stirred with saturated NaHCO3 (aq). The layers were separated and the aqueous layer was further extracted with CHCl3/MeOH. The combined organic layers were dried (MgSO4), filtered, and concentrated to yield product as an off-white foam.

Workup

  1. temperatureThe solution was cooled
  2. filtrationthe resulting white precipitate was collected by filtration
  3. dissolutionThe hydrobromide salt (9.6 g, 69%) was dissolved in CHCl3/MeOH
  4. customThe layers were separated
  5. extractionthe aqueous layer was further extracted with CHCl3/MeOH
  6. dry with materialThe combined organic layers were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto yield product as an off-white foam

Sources & evidence

ORD record
ord-d28f79854c6c4ab482df7cf5a4c5584a
Source dataset
uspto-grants-2006_05
Patent number
US07037530B2

Reaction notes

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