Hydrogen Bromide → Lasofoxifene

HRID 617283Notes

Reaction equation

HRID 617283 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 satd 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. 1H NMR (250 MHz, CDCl3): d 7.04 (m, 3H), 6.74 (m, 2H), 6.63 (d, J=8.3 Hz, 2H), 6.50 (m, 3H), 6.28 (d, J=8.6 Hz, 2H), 4.14 (d, J=4.9 Hz, 1H), 3.94 (t, J=5.3 Hz, 2H), 3.24 (dd, J=12.5, 4.1 Hz, 1H), 2.95 (m, 4H), 2.78 (m, 4H), 2.14 (m, 1H), 1.88 (m, 4H), 1.68 (m, 1H).

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-0c14871eb68e4e3c844d83247c06c0de
Source dataset
uspto-grants-1999_09
Patent number
US05948809

Reaction notes

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