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

HRID 1514775Notes

Reaction equation

HRID 1514775 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-e2a6f1970d4240758edfc5553ca9eb42
Source dataset
uspto-grants-2012_07
Patent number
US08222277B2

Reaction notes

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