Hydrochloric Acid → (2S,3aS,4R,9bR)-4-(4-Hydroxy-phenyl)-2-methyl-1,2,3,3a,4,9b-hexahydro-cyclopenta [c]chromen-8-ol

HRID 2118382ノート

反応式

HRID 2118382 の反応式
COC[O:4][C:5]1[CH:10]=[CH:9][C:8]([O:11]COC)=[CH:7][C:6]=1[C@@H:15]1[CH2:19][C@H:18]([CH3:20])[CH2:17][C@@H:16]1[C:21]([C:23]1[CH:28]=[CH:27][C:26]([O:29]COC)=[CH:25][CH:24]=1)=O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C([BH3-])#N.[Na+].Cl>CO.BrCOC1C(O)=CC=C(C)C=1.CCOC(C)=O>[OH:29][C:26]1[CH:25]=[CH:24][C:23]([C@H:21]2[C@H:16]3[CH2:17][C@@H:18]([CH3:19])[CH2:20][C@H:15]3[C:6]3[CH:7]=[C:8]([OH:11])[CH:9]=[CH:10][C:5]=3[O:4]2)=[CH:28][CH:27]=1

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 6101p-Toluenesulfonic acidHCID 5003444Sodium cyanoborohydrideHCID 59816181(1S,2R,4S)-[2-(2,5-Bis-methoxymethoxy-phenyl)-4-methyl-cyclopentyl]-(4-methoxymethoxy-phenyl)-methanone

生成物 1

HCID 9948127(2S,3aS,4R,9bR)-4-(4-Hydroxy-phenyl)-2-methyl-1,2,3,3a,4,9b-hexahydro-cyclopenta [c]chromen-8-ol収率 70%

試薬・触媒・溶媒 3

HCID 86612474Bromocreosol触媒HCID 887Methanol溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
50 °C

実験手順

To a solution of [2-(2,5-bis-methoxymethoxy-phenyl)-4-methyl-cyclopentyl]-(4-methoxymethoxy-phenyl)-methanone 10a (2.6 g, 5.8 mmol) in anhydrous methanol (232 mL) add p-toluenesulfonic acid (1.1 g, 5.8 mmol) and heat the resulting solution to 50° C. for 18 hours under nitrogen. Cool the reaction to ambient temperature and add bromocreosol green (10 mg) and sodium cyanoborohydride (1.82 g, 29.0 mmol). Add methanol saturated with HCl (gas) drop wise until yellow color is maintained. Stir the reaction one hour past the time when no more color change is observed. Quench the reaction with saturated sodium bicarbonate, add EtOAc, and wash the organic solution with sodium bicarbonate and brine. Dry the organic solution over sodium sulfate, concentrate in vacuo, and purify by flash chromatography (silica gel, 0-40% EtOAc/hexanes and 40% ethyl acetate/hexanes) to give 4-(4-Hydroxy-phenyl)-2-methyl-1,2,3,3a,4,9b-hexahydro-cyclopenta[c]chromen-8-ol 11a (1.2 g, 4.0 mmol, 70%). 1H NMR (δ, 400 MHz, MeOD) 7.23 (d, 2H, J=8.4 Hz), 6.77 (d, 2H, J=8.4 Hz), 6.68 (d, 1H, J=8.8 Hz), 6.54 (d, 1H, J=2.6 Hz), 6.50 (dd, 1H, J=8.6, 2.9 Hz), 3.45-3.38 (m, 1H), 2.63-2.55 (m, 1H), 2.52-2.43 (m, 1H), 1.96-1.84 (m, 1H), 1.41-1.32 (m, 1H), 1.23-1.07 (m, 2H), 0.87 (d, 3H, J=6.6 Hz). MS calcd. 295.1; found (electrospray, M−1) 295.1. HPLC (Zorbax C18 column; 10 to 100% CH3CN/H2O for 10 min then 100% CH3CN for 5 min; 1 mL/min; tr 10.35 min). HPLC (Chiralpak AD, 20-80% IPA/Heptane for 20 min; 1 mL/min; tR=4.37 min).

後処理

  1. temperatureCool
  2. customthe reaction to ambient temperature
  3. customthe reaction one hour past the time when no more color change
  4. customQuench
  5. customthe reaction with saturated sodium bicarbonate
  6. washwash the organic solution with sodium bicarbonate and brine
  7. dry with materialDry the organic solution over sodium sulfate
  8. concentrationconcentrate in vacuo
  9. custompurify by flash chromatography (silica gel, 0-40% EtOAc/hexanes and 40% ethyl acetate/hexanes)

出典と根拠

ORDレコード
ord-683a9e25e4fc4461a70349e3010f38e8
出典データセット
uspto-grants-2008_10
特許番号
US07442812B2

反応ノート

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