Hydrochloric Acid → 5-(4-(2-(Piperidin-1-yl)ethoxy)phenoxy)-6-(trifluoromethylsulfonyloxy)naphthalen-2-yl acetate

HRID 1513986Notes

Reaction equation

HRID 1513986 reaction equation
COC1C=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([O:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][N:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)=[CH:16][CH:15]=1)=[C:8]([O:29][S:30]([C:33]([F:36])([F:35])[F:34])(=[O:32])=[O:31])[CH:7]=[CH:6]2.Cl.CCOCC.B(Br)(Br)Br.C(=O)(O)[O-].[Na+].C(N(CC)C(C)C)(C)C.[C:61]([O:64][C:65](=O)[CH3:66])(=[O:63])[CH3:62]>C(Cl)Cl.CN(C)C1C=CN=CC=1>[N:23]1([CH2:22][CH2:21][O:20][C:17]2[CH:16]=[CH:15][C:14]([O:13][C:9]3[C:8]([O:29][S:30]([C:33]([F:36])([F:34])[F:35])(=[O:32])=[O:31])=[CH:7][CH:6]=[C:5]4[C:10]=3[CH:11]=[CH:12][C:65]([O:64][C:61](=[O:63])[CH3:62])=[CH:66]4)=[CH:19][CH:18]=2)[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 7918Acetic AnhydrideHCID 25134Boron tribromideHCID 81531DiisopropylethylamineHCID 516892Sodium Bicarbonate2×HCID 116133766-Methoxy-1-(4-(2-(piperidin-1-yl)ethoxy)phenoxy)naphthalen-2-yl trifluoromethanesulfonate

Product 1

HCID 583385445-(4-(2-(Piperidin-1-yl)ethoxy)phenoxy)-6-(trifluoromethylsulfonyloxy)naphthalen-2-yl acetateYield 100%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Charge a flask with trifluoro-methanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)-phenoxy]-naphthalen-2-yl ester (10.0 g, 19.0 mmol) and dissolve in methylene chloride (100 mL). Add 2M HCl in ether (19 mL, 38 mmol) and remove solvent in vacuo. Redissolve in dry methylene chloride (200 mL) and cool to 0° C. under nitrogen. Add BBr3 (9.0 mL, 95 mmol) slowly, and stir at 0° C. for 30 minutes. Pour reaction slowly into saturated aqueous sodium bicarbonate and extract with methylene chloride. Dry over sodium sulfate, filter and concentrate in vacuo. Dissolve crude material in methylene chloride (200 mL) and add N,N-diisopropylethylamine (16.5 mL, 95 mmol) and 4-dimethylaminopyridine (120 mg, 1.9 mmol) and stir at room temperature. Add acetic anhydride (3.6 mL, 38 mmol). Stir for 20 minutes and pour into saturated aqueous sodium bicarbonate. Extract with methylene chloride. Wash the organic layer with water, dry over sodium sulfate, filter and concentrate in vacuo to yield 10.5 g (100%) of acetic acid 5-[4-(2-piperidin-1-yl-ethoxy)-phenoxy]-6-trifluoromethanesulfonyloxy-naphthalen-2-yl ester.

Workup

  1. customremove solvent in vacuo
  2. dissolutionRedissolve in dry methylene chloride (200 mL)
  3. additionPour
  4. extractionextract with methylene chloride
  5. dry with materialDry over sodium sulfate
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. dissolutionDissolve crude material in methylene chloride (200 mL)
  9. stirringStir for 20 minutes
  10. extractionExtract with methylene chloride
  11. washWash the organic layer with water
  12. dry with materialdry over sodium sulfate
  13. filtrationfilter
  14. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-2101114bfc544ea48843a9e0c833c080
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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