Dichloromethane → Trifluoromethanesulfonic acid 1-[4-(2-azepan-1-yl-ethoxy)-phenoxy]-6-methoxy-naphthalen-2-yl ester

HRID 1513871Notes

Reaction equation

HRID 1513871 reaction equation
[F:1][C:2]([F:15])([F:14])[S:3]([O:6]S(C(F)(F)F)(=O)=O)(=[O:5])=[O:4].[N:16]1([CH2:23][CH2:24][O:25][C:26]2[CH:45]=[CH:44][C:29]([O:30][C:31]3[C:40]4[C:35](=[CH:36][C:37]([O:41][CH3:42])=[CH:38][CH:39]=4)[CH:34]=[CH:33][C:32]=3O)=[CH:28][CH:27]=2)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1.C(N(CC)CC)C.C(Cl)Cl>[Cl-].[Na+].O>[N:16]1([CH2:23][CH2:24][O:25][C:26]2[CH:27]=[CH:28][C:29]([O:30][C:31]3[C:40]4[C:35](=[CH:36][C:37]([O:41][CH3:42])=[CH:38][CH:39]=4)[CH:34]=[CH:33][C:32]=3[O:6][S:3]([C:2]([F:15])([F:14])[F:1])(=[O:5])=[O:4])=[CH:44][CH:45]=2)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 67749Trifluoromethanesulfonic anhydrideHCID 670047881-[4-(2-Azepan-1-yl-ethoxy)-phenoxy]-6-methoxy-naphthalen-2-ol

Product 1

HCID 57552539Trifluoromethanesulfonic acid 1-[4-(2-azepan-1-yl-ethoxy)-phenoxy]-6-methoxy-naphthalen-2-yl esterYield 100.2%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Procedure

Add trifluoromethanesulfonic anhydride (7 mL, 42 mmol) into a solution of 1-[4-(2-azepan-1-yl-ethoxy)-phenoxy]-6-methoxy-naphthalen-2-ol (15 g, 37 mmol), triethylamine (20 mL) and methylene chloride (500 mL) at −50° C. Warm the reaction mixture to room temperature and stir for 1 hour at that temperature. Cool the reaction mixture to −78° C. and add brine (20 ml). Warm the reaction to room temperature. Separate layer and wash the organic layer with saturated sodium bicarbonate solution (100 mL) and brine. Dry the organic layer with magnesium sulfate, filter and evaporate solvent under reduced pressure. Chromatograph the residue on a silica gel column eluting the material with a step gradient of methanol/dichloromethane (0 to 10%) to get 20 g (99%) of trifluoro-methanesulfonic acid 1-[4-(2-azepan-1-yl-ethoxy)-phenoxy]-6-methoxy-naphthalen-2-yl ester.

Workup

  1. temperatureCool the reaction mixture to −78° C.
  2. temperatureWarm
  3. customthe reaction to room temperature
  4. washSeparate layer and wash the organic layer with saturated sodium bicarbonate solution (100 mL) and brine
  5. dry with materialDry the organic layer with magnesium sulfate
  6. filtrationfilter
  7. customevaporate solvent under reduced pressure
  8. washChromatograph the residue on a silica gel column eluting the material with a step gradient of methanol/dichloromethane (0 to 10%)

Sources & evidence

ORD record
ord-10d44cae30744debb0a2c4d0c4790882
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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