Trimethylolethane → 3-Hydroxy-2-(hydroxymethyl)-2-methylpropyl (2S)-2-(6-methoxy(2-naphthyl))-propanoate

HRID 1374052

反応式

HRID 1374052 の反応式
[OH:1][CH2:2][C:3]([CH2:7][OH:8])([CH2:5][OH:6])[CH3:4].[CH3:9][O:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[CH:17]=[C:16]([C@H:21]([CH3:25])[C:22](O)=[O:23])[CH:15]=[CH:14]2.Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C>C(#N)C>[CH3:9][O:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[CH:17]=[C:16]([C@H:21]([CH3:25])[C:22]([O:1][CH2:2][C:3]([CH2:7][OH:8])([CH3:4])[CH2:5][OH:6])=[O:23])[CH:15]=[CH:14]2

参加物

6

反応物 4

HCID 6502TrimethylolethaneHCID 8471TriethylamineHCID 156391NaproxenHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

生成物 1

HCID 666248223-Hydroxy-2-(hydroxymethyl)-2-methylpropyl (2S)-2-(6-methoxy(2-naphthyl))-propanoate収率 66%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

To a stirred solution of 1,1,1-tris(hydroxymethyl)ethane (13.1 g, 109 mmol), (2S)-2-(6-methoxy(2-naphthyl))propanoic acid (naproxen, 5.00 g, 21.7 mmol), 1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride (4.80 g, 25 mmol), and N,N-dimethylaminopyridine (DMAP, 20 mg, catalytic amount) in acetonitrile (200 mL) was added triethylamine (4.2 mL, 30 mmol). The reaction mixture was stirred at ambient temperature for 25 hours, filtered, and the filtrate was concentrated to dryness. The residue was diluted with EtOAc, washed with 1N HCl (2×), saturated NaHCO3, and brine, dried over Na2SO4, filtered, and concentrated The resulting material was purified by crystallization (2×) from EtOAc/Hexanes (13 v:v) to give the title compound (4.72 g, 66% yield) as white flakes. Mp 105° C. 1H NMR (300 CDCl3) δ 7.72 (d, J=2.0 Hz, 1H), 769 (d J 25 Hz, 1H), 7.66 (s, 1H), 7.39 (dd, J=8.5, 1.7 Hz, 1H), 7.17–7.10 (m, 2H), 4.25 (d, J=11.3 Hz, 1H), 4.09 (d, J=11.3 Hz, 1H), 3.90 (s, 3H), 3.88 (q, J=7.1 Hz, 1H), 3.46–3.25 (m, 4H), 2.65–2.55 (m, 2H), 1.60 (d, J=7.1 Hz, 3H), 0.67 (s, 3H). 13C NMR (75 MHz, CDCl3) 8175.8, 157.7, 135.3, 133.8, 129.2, 128.9, 127.3, 126.0, 119.2, 105.6, 67.7. 67.5, 66.8, 55.3, 45.6, 40.9, 18.1, 16.7. LRMS (API-TIS) m/z 350.2 ((M+NH4)+).

後処理

  1. filtrationfiltered
  2. concentrationthe filtrate was concentrated to dryness
  3. additionThe residue was diluted with EtOAc
  4. washwashed with 1N HCl (2×), saturated NaHCO3, and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated The resulting material
  8. customwas purified by crystallization (2×) from EtOAc/Hexanes (13 v:v)

出典と根拠

ORDレコード
ord-010d92a984bb4090b01412b5671aab5d
出典データセット
uspto-grants-2007_01
特許番号
US07163958B2

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