Water → HCID 57707196, compound

HRID 1662483Notes

Reaction equation

HRID 1662483 reaction equation
[F:1][C:2]([F:19])([F:18])[CH2:3][CH2:4][C@@H:5]([C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([OH:17])[CH:12]=1)[CH2:6][C:7]([O:9][CH3:10])=[O:8].[OH:20][C:21]1[CH:22]=[C:23](B(O)O)[CH:24]=[CH:25][CH:26]=1.O1CCOCC1.O.[F:37][C:38]([F:49])([F:48])[CH2:39][CH2:40]/[CH:41]=[CH:42]/[C:43]([O:45][CH2:46][CH3:47])=[O:44]>CCOC(C)=O>[F:1][C:2]([F:18])([F:19])[CH2:3][CH2:4][C@@H:5]([C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([OH:17])[CH:12]=1)[CH2:6][C:7]([O:9][CH2:10][CH3:21])=[O:8].[F:37][C:38]([F:48])([F:49])[CH2:39][CH2:40][C@H:41]([C:23]1[CH:24]=[CH:25][CH:26]=[C:21]([OH:20])[CH:22]=1)[CH2:42][C:43]([O:45][CH2:46][CH3:47])=[O:44]

Participants

8

Reactant 5

HCID 962WaterHCID 312751,4-DioxaneHCID 2734359(3-hydroxyphenyl)boronic AcidHCID 21666955HCID 21666955, compoundHCID 67429232HCID 67429232, compound2×

Product 2

HCID 57707196HCID 57707196, compoundHCID 57707199HCID 57707199, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

Methyl (3R)-6,6,6-trifluoro-3-(3-hydroxyphenyl)hexanoate or methyl (3S)-6,6,6-trifluoro-3-(3-hydroxyphenyl)hexanoate (68). A mixture of 3-hydroxyphenylboronic acid (available from Aldrich) (1.8 g, 13 mmol) and hydroxy[(S)-BINAP]-rhodium(I) dimer (0.19 g, 0.13 mmol) in 1,4-dioxane (10 mL, 2.5 mmol) was sparged with N2. To the mixture were added water (1.0 mL, 2.5 mmol) and (E)-ethyl 6,6,6-trifluorohex-2-enoate 68.B (0.56 mL, 2.5 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 residue was purified by silica gel flash chromatography (0-25% EtOAc/hexane) to afford (R)-ethyl 6,6,6-trifluoro-3-(3-hydroxyphenyl)hexanoate and (S)-ethyl 6,6,6-trifluoro-3-(3-hydroxyphenyl)hexanoate 68 as a pale yellow oil (84% e.e.). The enantiomerically enriched mixture was further purified by chiral HPLC (Chiralcel OD, 3% i-PrOH/hexane, 220 nm) to afford 68 as a colorless oil (0.65 g, >99% e.e.). The R enantiomer is believed to be the major product used in the following steps.

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 residue was purified by silica gel flash chromatography (0-25% EtOAc/hexane)

Sources & evidence

ORD record
ord-d3739f43974842bfa837c229d14fbbb1
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Reaction notes

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