Triethylamine → 4-[1-(4'-tert-Butyl-biphenyl-4-ylamino)-3-methyl-butyl]-benzoic acid methyl ester

HRID 642806Notes

Reaction equation

HRID 642806 reaction equation
[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[CH:8][C:7]([C:10](=O)[CH2:11][CH:12]([CH3:14])[CH3:13])=[CH:6][CH:5]=1.[C:17]([C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)=[CH:23][CH:22]=1)([CH3:20])([CH3:19])[CH3:18].C(N(CC)CC)C.C([BH3-])#N.[Na+].[OH-].[Na+]>ClCCl.CO.[Ti](Cl)(Cl)(Cl)Cl>[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[CH:8][C:7]([CH:10]([NH:33][C:30]2[CH:29]=[CH:28][C:27]([C:24]3[CH:25]=[CH:26][C:21]([C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:22][CH:23]=3)=[CH:32][CH:31]=2)[CH2:11][CH:12]([CH3:14])[CH3:13])=[CH:6][CH:5]=1

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 201001574'-(1,1-Dimethylethyl)[1,1'-biphenyl]-4-amineHCID 56593012Methyl 4-(3-methylbutanoyl)benzoate

Product 1

HCID 674879154-[1-(4'-tert-Butyl-biphenyl-4-ylamino)-3-methyl-butyl]-benzoic acid methyl esterYield 83.6%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 4-(3-methyl-butyryl)-benzoic acid methyl ester (Preparation 4) (440 mg, 2 mmol) in dichloromethane (30 mL) is added 4′-tert-butyl-biphenyl-4-ylamine (Preparation 1) (450 mg, 2 mmol), and triethylamine (606 mg, 6 mmol). Titanium(IV) chloride in dichloromethane (1M, 1 mL) is added dropwise. The reaction is monitored by TLC. Once the starting material is consumed, the reaction is carefully quenched with sodium cyanoborohydride (377 mg, 6 mmol) in MeOH (5 mL) and stirred for 2 h. The reaction is adjusted to pH=13 with 5N NaOH, extracted with EtOAc, dried (Na2SO4), and concentrated under reduced pressure. The resulting residue is purified by silica gel chromatography, eluting with dichloromethane to afford 718 mg of the titled compound. 1H-NMR.

Workup

  1. customOnce the starting material is consumed
  2. extractionextracted with EtOAc
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue is purified by silica gel chromatography
  6. washeluting with dichloromethane

Sources & evidence

ORD record
ord-8827836bbbb644b89bb73509822a5dae
Source dataset
uspto-grants-2010_04
Patent number
US07696248B2

Reaction notes

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