Triethylamine → 3-(benzyloxy)-4-bromo-N-(prop-2-ynyl)-5-((2-(trimethylsilyl)ethoxy)-methoxy)benzamide

HRID 1027244Notes

Reaction equation

HRID 1027244 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:15]=[C:16]([O:19][CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[C:17]=1[Br:18])[C:12](O)=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH2:35]([NH2:38])[C:36]#[CH:37]>ClCCl.C(OCC)(=O)C.C(OCC)C>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:15]=[C:16]([O:19][CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[C:17]=1[Br:18])[C:12]([NH:38][CH2:35][C:36]#[CH:37])=[O:13])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 239041PropargylamineHCID 867106503-(Benzyloxy)-4-bromo-5-((2-(trimethylsilyl)ethoxy)methoxy)benzoic acid

Product 1

HCID 867106513-(benzyloxy)-4-bromo-N-(prop-2-ynyl)-5-((2-(trimethylsilyl)ethoxy)-methoxy)benzamideYield 97.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21584169Diethylether ethylacetateSolvent

Procedure

To a mixture of 3-(benzyloxy)-4-bromo-5-((2-(trimethylsilyl)ethoxy)methoxy)benzoic acid (6.142 g, 13.55 mmol) and Mukaiyama reagent (2-chloro-1-methylpyridinium iodide, 5.19 g, 20.3 mmol) in dichloromethane (135 mL) was added triethylamine (7.55 mL, 54.2 mmol). The solution was stirred for 10 minutes after which time propargylamine (1.74 mL, 27.1 mmol) was added. The solution was stirred overnight. The solution was diluted with 1:1 ethyl acetate/diethyl ether and washed with water, brine, dried over MgSO4 and concentrated. The crude product was purified by flash chromatography (40 g silica gel, gradient of ethyl acetate in dichloromethane) providing 3-(benzyloxy)-4-bromo-N-(prop-2-ynyl)-5-((2-(trimethylsilyl)ethoxy)-methoxy)-benzamide as an orange oil (6.49 g). MS (M+1)=492.2. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.28-7.55 (m, 5H) 7.13 (dd, J=11.37, 1.77 Hz, 2H) 6.23 (br. s., 1H) 5.34 (s, 2H) 5.20 (s, 2H) 4.22 (dd, J=5.05, 2.53 Hz, 2H) 3.81 (dd, J=9.09, 7.58 Hz, 2H) 2.28 (t, J=2.78 Hz, 1H) 0.91-1.00 (m, 2H) −0.03-0.03 (m, 9H).

Workup

  1. additionwas added
  2. washwashed with water, brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customThe crude product was purified by flash chromatography (40 g silica gel, gradient of ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-d629bd515d384d5b8837fc4104da4b16
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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