2,6-Lutidine → 3-Triisopropylsilanyloxy-cyclopentanecarboxylic acid ethyl ester

HRID 2176323Notes

Reaction equation

HRID 2176323 reaction equation
[CH2:1]([O:3][C:4]([CH:6]1[CH2:10][CH2:9][CH:8]([OH:11])[CH2:7]1)=[O:5])[CH3:2].N1C(C)=CC=CC=1C.FC(F)(F)S(O[Si:26]([CH:33]([CH3:35])[CH3:34])([CH:30]([CH3:32])[CH3:31])[CH:27]([CH3:29])[CH3:28])(=O)=O>ClCCl>[CH2:1]([O:3][C:4]([CH:6]1[CH2:10][CH2:9][CH:8]([O:11][Si:26]([CH:33]([CH3:35])[CH3:34])([CH:30]([CH3:32])[CH3:31])[CH:27]([CH3:29])[CH3:28])[CH2:7]1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 2724529Triisopropylsilyl trifluoromethanesulfonateHCID 53407781Ethyl 3-hydroxycyclopentanecarboxylate

Product 1

HCID 867061723-Triisopropylsilanyloxy-cyclopentanecarboxylic acid ethyl esterYield 97.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 3-hydroxy-cyclopentanecarboxylic acid ethyl ester (prepared as described in PCT Int. Appl. 2008131946, 3.180 g, 20.1 mmol) in dichloromethane (100 mL) was subsequently treated with 2,6-lutidine (4.7 mL, 40.2 mmol) and triisopropylsilyl trifluoromethanesulfonate (8.1 mL, 30.15 mmol). After stirring for 3.5 h, the reaction was quenched with pH 4 buffer. The aqueous layer was extracted with dichloromethane. The organics were combined, filtered through a phase separator and the volatiles were removed in vacuo. The residue was purified by silica gel chromatography using a 100 g Isolute cartridge eluted with a continuous gradient of iso-hexanes/diethyl ether 1:0 to 9:1 to afford the title compound (6.15 g, 97%) as a light yellow oil and as a 3.5:1 mixture of diastereoisomers. 1H NMR (300 MHz, CDCl3): δ 1.04-1.08 (m, 27H), 1.27 (t, J=7.1 Hz, 4H), 1.70-2.00 (m, 5.2H), 2.04-2.21 (m, 2.6H), 2.66-2.79 (m, 1H), 2.97-3.10 (m, 0.3H), 4.14 (q, J=7.1 Hz, 2.6H), 4.29-4.39 (m, 1H), 4.43-4.50 (m, 0.3H).

Workup

  1. customthe reaction was quenched with pH 4 buffer
  2. extractionThe aqueous layer was extracted with dichloromethane
  3. filtrationfiltered through a phase separator
  4. customthe volatiles were removed in vacuo
  5. customThe residue was purified by silica gel chromatography
  6. washeluted with a continuous gradient of iso-hexanes/diethyl ether 1:0 to 9:1

Sources & evidence

ORD record
ord-59e0ea7ce95b4eb5bfa9e3cdfa287111
Source dataset
uspto-grants-2015_06
Patent number
US09062092B2

Reaction notes

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