2-Bromoethanol → 2-Hydroxyethyl (2S)-2-(6-methoxy(2-naphthyl))-propanoate

HRID 414943Notes

Reaction equation

HRID 414943 reaction equation
[Na+].[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[CH:10]=[C:9]([C@H:14]([CH3:18])[C:15]([O-:17])=[O:16])[CH:8]=[CH:7]2.Br[CH2:20][CH2:21][OH:22].CCOCC.CCCCCC>CN(C=O)C.C(Cl)Cl>[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[CH:10]=[C:9]([C@H:14]([CH3:18])[C:15]([O:17][CH2:20][CH2:21][OH:22])=[O:16])[CH:8]=[CH:7]2

Participants

6

Reactant 3

HCID 108982-BromoethanolHCID 21584099Diethylether hexaneHCID 23681059Naproxen Sodium

Product 1

HCID 133457912-Hydroxyethyl (2S)-2-(6-methoxy(2-naphthyl))-propanoateYield 84.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of (2S)-2-(6-methoxy(2-naphthyl))propanoic acid sodium salt (10.9 g, 43.2 mmol) and 2-bromoethanol (27.11 g, 0.22 mol) in DMF (150 mL) was heated to 80° C. for 3.5 hours. The excess 2-bromoethanol and DMF were evaporated under vacuum at 60° C. The resulted crude material was dissolved in CH2Cl2 (400 mL) and washed with water (400 mL), saturated NaHCO3 (100mL), 3N HCl (100 mL), brine and dried over Na2SO4, filtered and concentrated. Trituration of the residue with ether/hexane gave the title compound as a white solid (9.97 g, 84% yield). m.p. 72-73° C. 1H NMR (300 MHz, CDCl3) δ 8.0-7.68 (m, 3H), 7.66-7.61 (m, 1H), 7.16-7.1 (m, 2H), 4.25-4.15 (m, 2H), 3.93 (s, 3H), 3.92 (q, J=7.2 Hz, 1H), 3.75-3.70 (m, 2H), 1.78 (br. t, 1H), 1.59 (d, J=7.2 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 174.7, 157.3, 135.2, 133.4, 129.9, 128.6, 126.9, 125.8, 125.6, 118.6, 105.3, 65.9, 60.3, 54.8, 45.0, 18.2. MS(API) m/z 275 (M+NH4)+.

Workup

  1. customThe excess 2-bromoethanol and DMF were evaporated under vacuum at 60° C
  2. customThe resulted crude material
  3. washwashed with water (400 mL), saturated NaHCO3 (100mL), 3N HCl (100 mL), brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-081599a41dfb47e8bc6a3985064aa969
Source dataset
uspto-grants-2012_01
Patent number
US08088762B2

Reaction notes

Loading…