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 732304노트

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HRID 732304 반응식
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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 86612474Bromocreosol촉매HCID 887Methanol용매2회HCID 8857Ethyl Acetate용매

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온도
50 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-ed38dc924f8e47f99dc270936f456bba
출처 데이터셋
uspto-grants-2009_09
특허 번호
US07585985B2

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