Ethyl bromoacetate → [3-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-phenylamino]-acetic acid ethyl ester

HRID 547857Notes

Reaction equation

HRID 547857 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]3[CH:18]=[C:19]([NH2:23])[CH:20]=[CH:21][CH:22]=3)=[CH:11][CH:10]=2)=[C:4]([O:24][CH3:25])[CH:3]=1.[CH2:26]([O:28][C:29](=[O:32])[CH2:30]Br)[CH3:27].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH2:26]([O:28][C:29](=[O:32])[CH2:30][NH:23][C:19]1[CH:20]=[CH:21][CH:22]=[C:17]([CH2:16][O:15][C:12]2[CH:11]=[CH:10][C:9]([C:5]3[CH:6]=[C:7]([F:8])[C:2]([F:1])=[CH:3][C:4]=3[O:24][CH3:25])=[CH:14][CH:13]=2)[CH:18]=1)[CH3:27]

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetateHCID 11430Potassium CarbonateHCID 671537683-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-phenylamine

Product 1

HCID 67153766[3-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-phenylamino]-acetic acid ethyl esterYield 44.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
80 °C

Procedure

To a vial containing 3-(4′,5′-difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-phenylamine (0.35 g, 1.0 mmol) dissolved in acetonitrile (1 mL) was added bromo-acetic acid ethyl ester (0.113 ml, 1.0 mmol) and potassium carbonate (167 mg, 1.2 mmol) and additional acetonitrile (5 mL). The vial was sealed and heated to 80° C. overnight. The reaction was partitioned between ethyl acetate (200 mL) and aqueous HCl (0.1 M, 200 mL). The organic layer was separated and the aqueous layer extracted with ethyl acetate (200 mL). The organic layers were washed with brine (100 mL), combined, dried over magnesium sulfate, concentrated, dissolved in a minimal amount of dichloromethane and purified by flash chromatography with a 0-30% ethyl acetate in hexanes gradient to yield [3-(4′,5′-difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-phenylamino]-acetic acid ethyl ester as a clear semisolid (190 mg, 44%). LC-MS (ES) calculated for C24H23F2NO4, 427.16; found m/z 428 [M+H]+.

Workup

  1. customThe vial was sealed
  2. customThe reaction was partitioned between ethyl acetate (200 mL) and aqueous HCl (0.1 M, 200 mL)
  3. customThe organic layer was separated
  4. extractionthe aqueous layer extracted with ethyl acetate (200 mL)
  5. washThe organic layers were washed with brine (100 mL)
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. dissolutiondissolved in a minimal amount of dichloromethane
  9. custompurified by flash chromatography with a 0-30% ethyl acetate in hexanes gradient

Sources & evidence

ORD record
ord-310d060f6f924a20bd02f6a635477d86
Source dataset
uspto-grants-2011_05
Patent number
US07939569B1

Reaction notes

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