N,N-Dimethylaniline → Tert-butyl 3-(4-((2'-((dimethylamino)carbonyl)biphenyl-3-yl)methoxy)phenyl)propanoate

HRID 2422299Notes

Reaction equation

HRID 2422299 reaction equation
[C:1]([O:5][C:6]([CH2:8][CH2:9][C:10]1[CH:32]=[CH:31][C:13]([O:14][CH2:15][C:16]2[CH:17]=[C:18]([C:22]3[C:23]([C:28](O)=[O:29])=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:19]=[CH:20][CH:21]=2)=[CH:12][CH:11]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:33][N:34](C)[C:35]1C=CC=CC=1.O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>C(OCC)(=O)C.C(=O)([O-])O.[Na+].CN(C)C=O>[CH3:33][N:34]([CH3:35])[C:28]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[C:18]1[CH:19]=[CH:20][CH:21]=[C:16]([CH2:15][O:14][C:13]2[CH:31]=[CH:32][C:10]([CH2:9][CH2:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[CH:11][CH:12]=2)[CH:17]=1)=[O:29]

Participants

8

Reactant 4

HCID 949N,N-DimethylanilineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 575418463'-[4-(2-Tert-butoxycarbonylethyl)phenoxymethyl]biphenyl-2-carboxylic acid

Product 1

HCID 23083025Tert-butyl 3-(4-((2'-((dimethylamino)carbonyl)biphenyl-3-yl)methoxy)phenyl)propanoate

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a mixture of 3′-[4-(2-tert-butoxycarbonylethyl)phenoxymethyl]biphenyl-2-carboxylic acid (0.24 g, 0.56 mmol), dimethylaniline (2M tetrahydrofuran solution, 0.42 mL, 0.84 mmol), 1-hydroxybenzotriazole monohydrate (0.13 g, 0.84 mmol) and N,N-dimethylformamide (6.0 mL) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.16 g, 0.84 mmol) at room temperature with stirring, and the mixture was stirred at the same temperature for 12 hrs. The reaction mixture was diluted with ethyl acetate, saturated aqueous sodium hydrogen carbonate, washed successively with 5% aqueous potassium hydrogensulfate solution and saturated brine, dried (anhydrous magnesium sulfate), and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=2/1-1/2) to give tert-butyl 3-(4-((2′-((dimethylamino)carbonyl)biphenyl-3-yl)methoxy)phenyl)propanoate as a colorless oil. This compound was dissolved in trifluoroacetic acid (2 mL), and the mixture was stirred at room temperature for 1 hr, and concentrated under reduced pressure. The residue was purified by preparative HPLC (gradient cycle A) to give the title compound (58 mg, yield 26%) as colorless crystals. MS (APCI−): 402 (M−H).

Workup

  1. stirringthe mixture was stirred at the same temperature for 12 hrs
  2. washwashed successively with 5% aqueous potassium hydrogensulfate solution and saturated brine
  3. dry with materialdried (anhydrous magnesium sulfate)
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=2/1-1/2)

Sources & evidence

ORD record
ord-300ac28a1de34807ba6fd9670e21b910
Source dataset
uspto-grants-2011_06
Patent number
US07960369B2

Reaction notes

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