Water → (R)-ethyl 3-cyclobutyl-3-(3-hydroxyphenyl)propanoate

HRID 1662498노트

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HRID 1662498 반응식
[CH:1]1([C@@H:5]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([OH:17])[CH:12]=2)[CH2:6][C:7]([O:9][CH3:10])=[O:8])[CH2:4][CH2:3][CH2:2]1.[CH:18]1([C@H](C2C=CC=C(O)C=2)CC(OC)=O)CCC1.[OH:35][C:36]1[CH:37]=[C:38](B(O)O)[CH:39]=[CH:40][CH:41]=1.O1CCOCC1.O.[CH:52]1(/[CH:56]=[CH:57]/[C:58]([O:60][CH2:61][CH3:62])=[O:59])[CH2:55][CH2:54][CH2:53]1>CCOC(C)=O>[CH:1]1([C@@H:5]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([OH:17])[CH:12]=2)[CH2:6][C:7]([O:9][CH2:10][CH3:18])=[O:8])[CH2:2][CH2:3][CH2:4]1.[CH:52]1([C@H:56]([C:38]2[CH:39]=[CH:40][CH:41]=[C:36]([OH:35])[CH:37]=2)[CH2:57][C:58]([O:60][CH2:61][CH3:62])=[O:59])[CH2:53][CH2:54][CH2:55]1

참가 물질

9

반응물 6

HCID 962WaterHCID 312751,4-DioxaneHCID 2734359(3-hydroxyphenyl)boronic AcidHCID 57706492(E)-Ethyl 3-cyclobutylacrylateHCID 67429527methyl (3S)-3-cyclobutyl-3-(3-hydroxyphenyl)propanoateHCID 67429925methyl (3R)-3-cyclobutyl-3-(3-hydroxyphenyl)propanoate

생성물 2

HCID 57707220(R)-ethyl 3-cyclobutyl-3-(3-hydroxyphenyl)propanoate수율 96%HCID 57707268(S)-ethyl 3-cyclobutyl-3-(3-hydroxyphenyl)propanoate

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

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온도
45 °C

실험 절차

Methyl (3S)-3-cyclobutyl-3-(3-hydroxyphenyl)propanoate or methyl (3R)-3-cyclobutyl-3-(3-hydroxyphenyl)propanoate (70). A mixture of 3-hydroxyphenylboronic acid (available from Aldrich) (2.2 g, 16 mmol) and hydroxy[(S)-BINAP]-rhodium(I) dimer (0.24 g, 0.16 mmol) in 1,4-dioxane (10 mL, 3.2 mmol) was sparged with N2. To the mixture were added water (1.0 mL, 3.2 mmol) and (E)-ethyl 3-cyclobutylacrylate 70.C (0.56 mL, 3.2 mmol). The resulting red-brown solution was warmed to 45° C. and stirred for 3 hours (sealed vial). The mixture was cooled to room temperature, diluted with EtOAc, washed with saturated aqueous NaHCO3 and brine, dried (MgSO4), and concentrated. The crude product was purified by silica gel flash chromatography (0-25% EtOAc/hexane) to afford (S)-ethyl 3-cyclobutyl-3-(3-hydroxyphenyl)propanoate or (R)-ethyl 3-cyclobutyl-3-(3-hydroxyphenyl)propanoate 70 as a pale yellow oil (0.77 g, 96%) (92% e.e.). The enantiomerically enriched mixture was further purified by chiral HPLC (Chiralcel OD, 3% i-PrOH/hexane, 220 nm) to afford 70 as a colorless oil (>99% e.e.).

후처리

  1. customwas sparged with N2
  2. custom(sealed vial)
  3. temperatureThe mixture was cooled to room temperature
  4. washwashed with saturated aqueous NaHCO3 and brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customThe crude product was purified by silica gel flash chromatography (0-25% EtOAc/hexane)

출처 및 근거

ORD 기록
ord-d94819da3f9645e1bf30120f49801ce2
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08030354B2

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