Sodium Hydroxide → 4-[1-(4'-Trifluoromethyl-biphenyl-4-yloxy)-propyl]-benzoic acid

HRID 1160876Notes

Reaction equation

HRID 1160876 reaction equation
C[O:2][C:3](=[O:30])[C:4]1[CH:9]=[CH:8][C:7]([CH:10]([O:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=3)=[CH:16][CH:15]=2)[CH2:11][CH3:12])=[CH:6][CH:5]=1.[OH-].[Na+]>C(O)C>[F:27][C:26]([F:28])([F:29])[C:23]1[CH:22]=[CH:21][C:20]([C:17]2[CH:16]=[CH:15][C:14]([O:13][CH:10]([C:7]3[CH:6]=[CH:5][C:4]([C:3]([OH:30])=[O:2])=[CH:9][CH:8]=3)[CH2:11][CH3:12])=[CH:19][CH:18]=2)=[CH:25][CH:24]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 671534634-[1-(4'-Trifluoromethyl-biphenyl-4-yloxy)-propyl]-benzoic acid methyl ester

Product 1

HCID 671535374-[1-(4'-Trifluoromethyl-biphenyl-4-yloxy)-propyl]-benzoic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 4-(1-hydroxy-propyl)-benzoic acid methyl ester (300 mg, 1.55 mmol) in toluene (10 mL) is added 1, 1′-(azodicarbonyl)dipiperidine (ADDP, 585 mg, 2.32 mmol) at 0° C., followed by the addition of tributylphosphine (0.58 mL, 2.32 mmol) and 4′-trifluoromethyl-biphenyl-4-ol (442 mg, 1.86 mmol). The reaction mixture is warmed up to room temperature and stirred overnight. The mixture is loaded on silica gel, eluted with hexanes with a gradient from 0% of ethyl acetate to 50% of ethyl acetate giving 4-[1-(4′-trifluoromethyl-biphenyl-4-yloxy)-propyl]-benzoic acid methyl ester. The ester product is taken into ethanol (2 mL), treated with sodium hydroxide (5N aqueous, 1 mL) for 3 hours at room temperature. The mixture is concentrated, diluted with ethyl acetate, acidified with 5 N HCl (1.1 mL), extracted with ethyl acetate. The organic layers are dried and concentrated giving 4-[1-(4′-trifluoromethyl-biphenyl-4-yloxy)-propyl]-benzoic acid (570 mg).

Workup

  1. concentrationThe mixture is concentrated
  2. additiondiluted with ethyl acetate
  3. extractionextracted with ethyl acetate
  4. customThe organic layers are dried
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-f0122d97a06449f7b579873defab9b28
Source dataset
uspto-grants-2010_10
Patent number
US07816557B2

Reaction notes

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