Hydrogen Bromide → 3-[(R*)-1-((S)-6-Benzyloxy-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-piperidin-3-yl]-phenol

HRID 2365974Notes

Reaction equation

HRID 2365974 reaction equation
[CH2:1]([O:8][C:9]1[CH:24]=[CH:23][C:12]2[O:13][C@@H:14]([CH2:17]OS(C)(=O)=O)[CH2:15][O:16][C:11]=2[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:25]1[CH2:30][CH2:29][CH2:28][C@H:27]([C:31]2[CH:32]=[C:33]([OH:37])[CH:34]=[CH:35][CH:36]=2)[CH2:26]1.Br.C([O-])(O)=O.[Na+]>C(#N)C>[CH2:1]([O:8][C:9]1[CH:24]=[CH:23][C:12]2[O:13][C@@H:14]([CH2:17][N:25]3[CH2:30][CH2:29][CH2:28][C@H:27]([C:31]4[CH:32]=[C:33]([OH:37])[CH:34]=[CH:35][CH:36]=4)[CH2:26]3)[CH2:15][O:16][C:11]=2[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 260Hydrogen BromideHCID 516892Sodium BicarbonateHCID 12937952Phenol, 3-(3R)-3-piperidinyl-HCID 86644715(R)-(6-(benzyloxy)-2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methyl methanesulfonate

Product 1

HCID 251751693-[(R*)-1-((S)-6-Benzyloxy-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-piperidin-3-yl]-phenol

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of methanesulfonic acid (R)-6-benzyloxy-2,3-dihydrobenzo[1,4]dioxin-2-ylmethyl ester (129 mg, 0.368 mmol) and (R*)-3-(piperidin-3-yl)phenol.HBr (100 mg, 0.387 mmol) in acetonitrile was added solid KI (40 mg) and NaHCO3 (98 mg 1.162 mmol). The mixture was heated under microwave irradiation at 150° C. for 1 h. Solid material was filtered and the solvent was evaporated under reduced pressure. The residue was dissolved to DCM and washed twice with water and brine. The organic phase was dried (Na2SO4), and evaporated in vacuo. The residue was purified by flash column chromatography (EtOAc/heptane) to give the desired product (66.2 mg).

Workup

  1. filtrationSolid material was filtered
  2. customthe solvent was evaporated under reduced pressure
  3. dissolutionThe residue was dissolved to DCM
  4. washwashed twice with water and brine
  5. dry with materialThe organic phase was dried (Na2SO4)
  6. customevaporated in vacuo
  7. customThe residue was purified by flash column chromatography (EtOAc/heptane)

Sources & evidence

ORD record
ord-27d85d8103af40de9ac9a82c3d93f562
Source dataset
uspto-grants-2014_04
Patent number
US08697723B2

Reaction notes

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