Methanol → 6-Methoxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-ol

HRID 748935Notes

Reaction equation

HRID 748935 reaction equation
C[O:2][C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([O:13][CH3:14])[CH:9]=2)[C:4]=1[C:15]([C:17]1[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][N:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)=[CH:19][CH:18]=1)=[O:16].N#N.B(Cl)(Cl)Cl.CO.C([O-])(O)=O.[Na+]>C(Cl)Cl>[OH:2][C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([O:13][CH3:14])[CH:9]=2)[C:4]=1[C:15]([C:17]1[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][N:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)=[CH:19][CH:18]=1)=[O:16]

Participants

7

Reactant 5

HCID 887MethanolHCID 947NitrogenHCID 25135Boron TrichlorideHCID 516892Sodium BicarbonateHCID 11654660(2,6-Dimethoxy-naphthalen-1-yl)-[4-(2-piperidin-1-yl-ethoxy)phenyl]-methanone

Product 1

HCID 219316286-Methoxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-ol

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
5 °C

Procedure

Dissolve (2,6-dimethoxy-naphthalen-1-yl)-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone in CH2Cl2 (10 volume eq.) in a 3-neck round bottom flask equipped with a pressure equalizing addition funnel, stirbar, and N2 source. Cool the flask in an ice/brine bath and add 1.0 M BCl3 solution in CH2Cl2 (1.2 eq.) dropwise. The reaction solution turns dark red and the temperature initially increases to 5° C. After about 1 hour, quench the reaction with methanol (5 eq.) and allow to warm to room temperature. Dilute the organic solution with CH2Cl2 (one volume eq.) and add a 1.0 M NaHCO3 solution (5 volume eq.) and stir for one hour. Separate the aqueous and organic layers. Wash the aqueous layer with CH2Cl2 (one volume) and combine the organic layers. Wash with saturated. NH4Cl and dry over Na2SO4. Purify the product via column chromatography (50/1 silica gel) eluting with CH2Cl2/hexanes (3/1) to yield (2-hydroxy-6-methoxy-naphthalen-1-yl)-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone.

Workup

  1. customequipped with a pressure
  2. additionaddition funnel
  3. temperatureCool the flask in an ice/brine bath
  4. customquench
  5. temperatureto warm to room temperature
  6. customSeparate the aqueous and organic layers
  7. washWash the aqueous layer with CH2Cl2 (one volume)
  8. washWash with saturated
  9. dry with materialNH4Cl and dry over Na2SO4
  10. customPurify the product via column chromatography (50/1 silica gel)
  11. washeluting with CH2Cl2/hexanes (3/1)

Sources & evidence

ORD record
ord-e46d246f6be9443fb988863166e9307e
Source dataset
uspto-grants-2008_07
Patent number
US07399867B2

Reaction notes

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