Sodium Carbonate → [2-(2-Hydroxymethyl-phenyl)-6-methoxy-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone

HRID 916862Notes

Reaction equation

HRID 916862 reaction equation
C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[CH3:20][O:21][C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][CH:31]=1)[C:28]([C:32](=[O:48])[C:33]1[CH:38]=[CH:37][C:36]([O:39][CH2:40][CH2:41][N:42]3[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]3)=[CH:35][CH:34]=1)=[C:27](OS(C(F)(F)F)(=O)=O)[CH:26]=[CH:25]2.C([O-])([O-])=O.[Na+].[Na+].OB1[C:68]2[CH:69]=[CH:70][CH:71]=[CH:72][C:67]=2[CH2:66][O:65]1>COCCOC.C(Cl)Cl.CC([O-])=O.CC([O-])=O.[Pd+2]>[OH:65][CH2:66][C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][C:68]=1[C:27]1[CH:26]=[CH:25][C:24]2[C:29](=[CH:30][CH:31]=[C:22]([O:21][CH3:20])[CH:23]=2)[C:28]=1[C:32]([C:33]1[CH:34]=[CH:35][C:36]([O:39][CH2:40][CH2:41][N:42]2[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]2)=[CH:37][CH:38]=1)=[O:48]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 4037881-Hydroxy-2,1-benzoxaboroleHCID 11685250Trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)benzoyl]-naphthalen-2-yl ester

Product 1

HCID 17987067[2-(2-Hydroxymethyl-phenyl)-6-methoxy-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanoneYield 31.4%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

Add Pd(OAc)2 (15 mg, 0.07 mmol) and Ph3P (47 mg, 0.18 mmol) to a stirred solution of trifluoro-methanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester (600 mg, 1.1 mmol) in DME at r.t. Add Na2CO3 solution (2 mL of 2 M) followed by 1-hydroxy-2,1-benzoxaborolane (200 mg, 1.5 mmol). Stir at r.t. for 2 h and heat gently (˜50° C.) for 6 h. Dilute with CH2Cl2 and wash with water and brine, dry over MgSO4, filter and concentrate. Purify the crude product by flash chromatography (0-5% (2M NH3 in MeOH)/CH2Cl2 to yield [2-(2-hydroxymethyl-phenyl)-6-methoxy-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone (171 mg, 31%).

Workup

  1. temperatureheat gently (˜50° C.) for 6 h
  2. washwash with water and brine
  3. dry with materialdry over MgSO4
  4. filtrationfilter
  5. concentrationconcentrate
  6. customPurify the crude product by flash chromatography (0-5% (2M NH3 in MeOH)/CH2Cl2

Sources & evidence

ORD record
ord-c0e43aa3c1134ab791632e9207a7f403
Source dataset
uspto-grants-2007_09
Patent number
US07271264B2

Reaction notes

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