Ethanol → (2'-Amino-biphenyl-3-yl)-acetic acid methyl ester

HRID 383602

Reaction equation

HRID 383602 reaction equation
N#N.C(O)C.[NH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1B(O)O.[CH3:16][O:17][C:18](=[O:27])[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22](Br)[CH:21]=1>C1(C)C=CC=CC=1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:16][O:17][C:18](=[O:27])[CH2:19][C:20]1[CH:25]=[C:24]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[NH2:6])[CH:23]=[CH:22][CH:21]=1

Participants

7

Reactant 4

HCID 702EthanolHCID 947NitrogenHCID 2773216(2-Aminophenyl)boronic acidHCID 11746402Methyl 2-(3-bromophenyl)acetate

Product 1

HCID 16116037(2'-Amino-biphenyl-3-yl)-acetic acid methyl esterYield 106.8%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
100 °C

Procedure

(The following reaction is done in an oxygenfree N2 atmosphere.) Add ethanol (0.8 mL), Tetrakis-(triphenylphosphine)-palladium(0) (30 mg, 2.2 mol %) and Na2CO3 decahydrate (944 mg, 3.30 mmol; presolved in 1.2 mL H2O) subsequently to dissolved 2-Amino-benzeneboronic acid (70) (201 mg, 1.30 mmol) in toluene (6.0 mL). Degas the reaction mixture for 5 times and flood with N2 again. Add (3-Bromo-phenyl)-acetic acid methyl ester (69) (270 mg, 1.18 mmol) in toluene (6.0 mL), degas again (5 times) and stir the reaction solution overnight at 100° C. Partition the reaction solution between EtOAc and brine (1+1) and extract the separated aqueous layer 3 times with EtOAc. Wash combined organic layer with brine and dry with Na2SO4. Remove solvent under reduced pressure and purify the crude product by preparative radial chromatography (silica gel 60 PF, CyH/EtOAc 3+1) to obtain (2′-Amino-biphenyl-3-yl)-acetic acid methyl ester (71) as an orange oil (304 mg, 81%). 1H NMR (400 MHz, CDCl3): 3.66 (s, 2H); 3.69 (s, 3H); 3.62-3.86 (br.s, 2H); 6.75 (d, 1H, J=8.1 Hz); 6.80 (t, 1H, J=7.3 Hz); 7.11 (d, 1 H, J=7.3 Hz); 7.15 (d, 1H, J=8.1 Hz); 7.22-7.26 (br.m, 1H); 7.32-7.42 (m, 3H).

Workup

  1. custom(The following reaction
  2. customDegas the reaction mixture for 5 times and flood with N2 again
  3. customPartition the reaction solution between EtOAc and brine (1+1)
  4. extractionextract the separated aqueous layer 3 times with EtOAc
  5. washWash
  6. dry with materialdry with Na2SO4
  7. customRemove solvent under reduced pressure and purify the crude product by preparative radial chromatography (silica gel 60 PF, CyH/EtOAc 3+1)

Sources & evidence

ORD record
ord-2e00f144eb2a42b98629dc467dee78b7
Source dataset
uspto-grants-2013_02
Patent number
US08367677B2

Linked notes

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