D-Camphorsulfonic Acid → (S)-methyl 2-((S)-1-((4-methoxybenzyl)oxy)ethyl)-5-methylhexanoate

HRID 1770368Notes

Reaction equation

HRID 1770368 reaction equation
[OH:1][C@H:2]([C@H:4]([CH2:9][CH2:10][CH:11]([CH3:13])[CH3:12])[C:5]([O:7][CH3:8])=[O:6])[CH3:3].CC1(C)[C@@H]2CC[C@@]1(CS(O)(=O)=O)C(=O)C2.ClC(Cl)(Cl)C(=N)O[CH2:33][C:34]1[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=1>C(Cl)Cl>[CH3:41][O:40][C:37]1[CH:38]=[CH:39][C:34]([CH2:33][O:1][C@H:2]([C@H:4]([CH2:9][CH2:10][CH:11]([CH3:13])[CH3:12])[C:5]([O:7][CH3:8])=[O:6])[CH3:3])=[CH:35][CH:36]=1

Participants

5

Reactant 3

HCID 65617D-Camphorsulfonic AcidHCID 110872634-Methoxybenzyl 2,2,2-TrichloroacetimidateHCID 118194664(S)-methyl 2-((S)-1-hydroxyethyl)-5-methylhexanoate

Product 1

HCID 118194659(S)-methyl 2-((S)-1-((4-methoxybenzyl)oxy)ethyl)-5-methylhexanoateYield 77%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-methyl 2-((S)-1-hydroxyethyl)-5-methylhexanoate (5.00 g, 26.6 mmol) and ((1S,4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl)methanesulfonic acid (camphorsulfonic acid, CSA; 0.617 g, 2.66 mmol) in DCM (53.1 mL) was added 4-methoxybenzyl 2,2,2-trichloroacetimidate (8.27 mL, 39.8 mmol) at 0° C. The reaction mixture was removed from the cold bath and stirred at room temperature for 17 h. Hexane (50 mL) was added to the reaction and the precipitate was removed by filtration. The solids were washed with hexanes (2×10 mL), Celite® (2 scoopula tip-fulls) was added to the combined filtrate and washes, and the solvent was removed under reduced pressure. The resulting adsorbed material was directly loaded onto a column and purified using flash column chromatography (80 g SiO2, 0→35% EtOAc/hexanes) to afford the title compound (6.3 g, 20.4 mmol, 77%) as a colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.24-7.16 (m, 2H), 6.89-6.79 (m, 2H), 4.49 (d, J=11.2 Hz, 1H), 4.33 (d, J=11.1 Hz, 1H), 3.75 (s, 3H), 3.74-3.62 (m, 4H), 2.49 (ddd, J=10.7, 8.2, 4.0 Hz, 1H), 1.62-1.40 (m, 3H), 1.23-1.16 (m, 3H), 1.16-1.03 (m, 2H), 0.87 (d, J=3.9 Hz, 3H), 0.85 (d, J=3.9 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 175.03, 159.10, 130.63, 129.14, 113.62, 76.16, 70.71, 55.11, 52.64, 51.25, 36.58, 27.97, 26.00, 22.69, 22.17, 17.08; ESIMS m/z 331 ([M+Na]+).

Workup

  1. customThe reaction mixture was removed from the cold bath
  2. additionHexane (50 mL) was added to the reaction
  3. customthe precipitate was removed by filtration
  4. washThe solids were washed with hexanes (2×10 mL), Celite® (2 scoopula tip-fulls)
  5. additionwas added to the combined filtrate and washes
  6. customthe solvent was removed under reduced pressure
  7. custompurified

Sources & evidence

ORD record
ord-c33200089daf434cb1aba83d99804c0a
Source dataset
uspto-grants-2016_02
Patent number
US09247741B2

Reaction notes

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