Ethanethiol → HCID 11599362、化合物

HRID 1716186ノート

反応式

HRID 1716186 の反応式
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][S:10][CH:11]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][O:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][S:32]([CH3:35])(=[O:34])=[O:33])=[CH:27][CH:26]=3)=[CH:18][CH:17]=2)[C:12](O)=[O:13])=[CH:4][CH:3]=1.[Cl-].ClC=[N+](C)C.[CH2:42]([SH:44])[CH3:43].[OH-].[Na+]>C(OCC)(=O)C.P([O-])([O-])([O-])=O>[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][S:10][CH:11]([CH2:15][C:16]2[CH:17]=[CH:18][C:19]([CH2:22][CH2:23][O:24][C:25]3[CH:26]=[CH:27][C:28]([O:31][S:32]([CH3:35])(=[O:33])=[O:34])=[CH:29][CH:30]=3)=[CH:20][CH:21]=2)[C:12](=[O:13])[S:44][CH2:42][CH3:43])=[CH:4][CH:3]=1

参加物

7

反応物 4

HCID 6343EthanethiolHCID 14798Sodium HydroxideHCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 102179842-{[2-(4-Hydroxyphenyl)ethyl]thio}-3-[4-(2-{4-[(methylsulfonyl)oxy]-phenoxy}ethyl)phenyl]propanoic acid

生成物 1

HCID 11599362HCID 11599362、化合物収率 81%

試薬・触媒・溶媒 2

HCID 1061Phosphate溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
2.5 °C

実験手順

A solution of racemic 2-{[2-(4-hydroxyphenyl)ethyl]thio}-3-[4-(2-{4-[(methylsulfonyl)oxy]phenoxy}ethyl)phenyl]propanoic acid (45 g @ 80% strength, containing 8% wt/wt benzoic acid, 70 mmol) in ethyl acetate (225 mL, 5 vol) was cooled to 0-5° C. Solid chloromethylene-dimethylammonium chloride (Vilsmeier reagent @ 95% strength, 20.6 g, 161 mmol, 2.3 eq) was added in 4 equal portions over 1.5 hours maintaining a temperature of 0-5° C. The resulting turbid mixture was stirred at the same temperature for 2.5 hours and was subsequently added dropwise to an ice-cold vigorously stirred solution of ethanethiol (7.8 mL, 105 mmol, 1.5 eq.) in aqueous phosphate buffer (pH 7,200 mL). The pH was constantly monitored and kept between 6 and 7.5 by simultaneous addition of 32% NaOH solution. After 30 minutes at low temperature, the batch was allowed to warm to ambient temperature overnight. The organic phase was separated, dried (MgSO4) and concentrated in vacuo to give the crude product as brown oil (43.82 g, 114%). The crude compound was purified by flash chromatography (20:80 to 50:50 EtOAc:iso-hexane; silica) to yield the title compound as a pale yellow oil (31.5 g, 81%). HPLC (Rt 11.6 min); m.p. oil; 1H NMR (400 MHz, d6-DMSO) δ 9.19 (1H, s), 7.18-7.28 (4H, m), 7.14 (2H, d, J=8.1 Hz), 7.00-6.94 (4H, m), 6.65 (2H, d, J=8.4 Hz), 4.15 (2H, t, J=6.8 Hz), 3.87-3.83 (1H, m), 3.29 (3H, s), 3.08 (1H, dd, J=14.0, 8.4 Hz) 2.98 (2H, t, J=6.8 Hz), 2.87 (1H, dd, J=14.0, 7.0 Hz), 2.80-2.67 (4H, m), 2.66-2.60 (2H, m), 1.08 (3H, t, J=7.2 Hz); 13C NMR (100.6 MHz, d6-DMSO) δ 198.14, 157.15, 155.73, 142.45, 136.37, 135.52, 130.14, 129.34, 129.22, 129.07, 123.28, 115.39, 115.04, 68.51, 55.29, 37.14, 36.88, 34.41, 34.34, 32.78, 22.98 and 14.53.

後処理

  1. waitAfter 30 minutes at low temperature
  2. temperatureto warm to ambient temperature overnight
  3. customThe organic phase was separated
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customto give the crude product as brown oil (43.82 g, 114%)
  7. customThe crude compound was purified by flash chromatography (20:80 to 50:50 EtOAc:iso-hexane; silica)

出典と根拠

ORDレコード
ord-ee3e025cb24f41ecb9463b474e5d7a1a
出典データセット
uspto-grants-2010_09
特許番号
US07803586B2

反応ノート

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