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

HRID 1662498Notes

Reaction equation

HRID 1662498 reaction equation
[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

Participants

9

Reactant 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

Product 2

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

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

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.).

Workup

  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)

Sources & evidence

ORD record
ord-d94819da3f9645e1bf30120f49801ce2
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Reaction notes

Loading…