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

HRID 916860Notes

Reaction equation

HRID 916860 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-olYield 87%

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 equivalents) 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 equivalents) dropwise. The reaction solution turns dark red and the temperature initially increases to 5° C. Within one hour, all starting material is consumed, as determined by TLC (1:1, Ether:Petroleum Ether). Quench the reaction with methanol (5 equivalents) and allow to warm to room temperature. Dilute the organic solution with CH2Cl2 (one volume equivalent) and add to a 1.0 M NaHCO3 solution (5 volume equivalents) and stir for one hour. Separate the aqueous and organic layers. Wash the aqueous layer with CH2Cl2 (one volume) and the combine 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 (typical yield 87%).

Workup

  1. customequipped with a pressure
  2. additionaddition funnel
  3. temperatureCool the flask in an ice/brine bath
  4. customall starting material is consumed
  5. customQuench
  6. temperatureto warm to room temperature
  7. customSeparate the aqueous and organic layers
  8. washWash the aqueous layer with CH2Cl2 (one volume)
  9. washthe combine organic layers, wash with saturated NH4Cl
  10. dry with materialdry over Na2SO4
  11. customPurify the product via column chromatography (50/1 silica gel)
  12. washeluting with CH2Cl2/Hexanes (3/1)

Sources & evidence

ORD record
ord-5c43c31cc77c4d55b2c605f498c3d522
Source dataset
uspto-grants-2007_09
Patent number
US07271264B2

Reaction notes

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