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

HRID 1873630Notes

Reaction equation

HRID 1873630 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 (100 mL), 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 (100 mL), 3N HCl (100 mL), brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-b493b46160174833b3d0f83246cc8a65
Source dataset
uspto-grants-2012_11
Patent number
US08304409B2

Reaction notes

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