4-tert-Butylbenzaldehyde → Tert-butyl 2-(3-((4-tert-butylbenzylamino)methyl)phenoxy)acetate

HRID 2300538Notes

Reaction equation

HRID 2300538 reaction equation
[C:1]([O:5][C:6](=[O:17])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][NH2:16])[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[C:18]([C:22]1[CH:29]=[CH:28][C:25]([CH:26]=O)=[CH:24][CH:23]=1)([CH3:21])([CH3:20])[CH3:19].[BH4-].[Na+].C(=O)(O)[O-].[Na+]>CO.O>[C:1]([O:5][C:6](=[O:17])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][NH:16][CH2:26][C:25]2[CH:28]=[CH:29][C:22]([C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:23][CH:24]=2)[CH:10]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 703244-tert-ButylbenzaldehydeHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 20758042t-Butyl [3-(aminomethyl)phenoxy]acetate

Product 1

HCID 20758041Tert-butyl 2-(3-((4-tert-butylbenzylamino)methyl)phenoxy)acetate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of (3-aminomethyl-phenoxy)-acetic acid tert-butyl ester prepared in Step C of Preparation 20, (0.497 g, 2.09 mmol) in MeOH (8 mL) was added 4-tert-butylbenzaldehyde (0.33 mL, 1.97 mmol), and the mixture was stirred at room temperature for 2 h. The solution was cooled to 0° C. and sodium borohydride (0.119 g, 3.15 mmol) was added in one portion. The mixture was stirred for 10 min, and a 1:1 solution of water:aqueous saturated sodium bicarbonate was added to the solution. The product was extracted into CH2Cl2 (3×) and the combined organic solutions were dried (MgSO4) and concentrated in vacuo. The product was purified via silica gel chromatography (EtOAc followed by 5% MeOH in CH2Cl2) to give the title compound of Step A (0.691 g) as a clear oil. 1H NMR (400 MHz, CDCl3) δ 7.30-7.38 (m, 2H), 7.19-7.28 (m, 3H), 6.87-6.96 (m, 2H), 6.77 (d, 1H), 4.50 (s, 2H), 3.77 (s, 2H), 3.75 (s, 2H), 1.46 (s, 9H), 1.30 (s, 9H); MS 384 (M+1).

Workup

  1. temperatureThe solution was cooled to 0° C.
  2. stirringThe mixture was stirred for 10 min
  3. extractionThe product was extracted into CH2Cl2 (3×)
  4. dry with materialthe combined organic solutions were dried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe product was purified via silica gel chromatography (EtOAc followed by 5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-f4192002d0794c3f9c87d2e33bc83b59
Source dataset
uspto-grants-2002_12
Patent number
US06498172B1

Reaction notes

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