Diisopropylethylamine → ethyl 2-((R)-1-((S)-2-(tert-butyldimethylsilyloxy)-2-(4-cyanophenyl)ethyl)piperidin-3-yl)acetate

HRID 1948499Notes

Reaction equation

HRID 1948499 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C@H:9]([OH:23])[CH2:10][N:11]2[CH2:16][CH2:15][CH2:14][C@H:13]([CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:12]2)=[CH:5][CH:4]=1)#[N:2].CCN(C(C)C)C(C)C.FC(F)(F)S(O[Si:39]([C:42]([CH3:45])([CH3:44])[CH3:43])([CH3:41])[CH3:40])(=O)=O>C(Cl)Cl>[Si:39]([O:23][C@@H:9]([C:6]1[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:8][CH:7]=1)[CH2:10][N:11]1[CH2:16][CH2:15][CH2:14][C@H:13]([CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:12]1)([C:42]([CH3:45])([CH3:44])[CH3:43])([CH3:41])[CH3:40]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 58374148ethyl 2-((R)-1-((S)-2-(4-cyanophenyl)-2-hydroxyethyl)piperidin-3-yl)acetate

Product 1

HCID 66955124ethyl 2-((R)-1-((S)-2-(tert-butyldimethylsilyloxy)-2-(4-cyanophenyl)ethyl)piperidin-3-yl)acetateYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of (18C)-isomer A, ethyl 2-((R)-1-((S)-2-(4-cyanophenyl)-2-hydroxyethyl)piperidin-3-yl)acetate (6.00 g, 18.96 mmol) and DIPEA (5.96 ml, 34.1 mmol) in DCM (63 mL) was added tert-butyldimethylsilyl trifluoromethane-sulfonate (5.67 ml, 24.65 mmol) slowly. The reaction was monitored with HPLC and the reaction was complete in 2 hours. The reaction mixture (a light brown solution) was quenched with water, the aqueous layer was extracted twice with DCM. The organic phase was combined, dried with Na2SO4, filtered, and concentrated. The crude material was purified with on a silica gel cartridge (330 g silica, 10-30% EtOAc/hexanes gradient) to give ethyl 2-((R)-1-((S)-2-(tert-butyldimethylsilyloxy)-2-(4-cyanophenyl)ethyl)piperidin-3-yl)acetate (8 g, 18.58 mmol, 98% yield).

Workup

  1. customThe reaction mixture (a light brown solution) was quenched with water
  2. extractionthe aqueous layer was extracted twice with DCM
  3. dry with materialdried with Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified with on a silica gel cartridge (330 g silica, 10-30% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-24c4a4c9c9774430a937175e0cc9b909
Source dataset
uspto-grants-2013_03
Patent number
US08399451B2

Reaction notes

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