Diisopropylethylamine → HCID 58374102, compound

HRID 1948481Notes

Reaction equation

HRID 1948481 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C@H:9]([OH:22])[CH2:10][N:11]2[CH2:16][CH2:15][CH2:14][C@H:13]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:12]2)=[CH:5][CH:4]=1)#[N:2].CCN(C(C)C)C(C)C.FC(F)(F)S(O[Si:38]([C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:40])[CH3:39])(=O)=O>C(Cl)Cl>[Si:38]([O:22][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]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:12]1)([C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:40])[CH3:39]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 58374092HCID 58374092, compound

Product 1

HCID 58374102HCID 58374102, compoundYield 95%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of (S)-ethyl 1-((S)-2-(4-cyanophenyl)-2-hydroxyethyl)piperidine-3-carboxylate (17.0 g, 56.2 mmol) and DIPEA (17.68 ml, 101 mmol) in CH2Cl2 (187 mL) was added tert-butyldimethylsilyl trifluoromethanesulfonate (16 ml, 69.6 mmol) slowly. The reaction was monitored with HPLC. The reaction completed in 2 hours. The reaction mixture (a light brown solution) was quenched with water, the aqueous layer was extracted with DCM. The organic phase was combined and dried with Na2SO4. After concentration, the crude material was further purified on a silica gel cartridge (330 g silica, 10-30% EtOAc/hexanes gradient) to afford a purified product (S)-ethyl 1-((S)-2-(tert-butyldimethylsilyloxy)-2-(4-cyanophenyl)ethyl)piperidine-3-carboxylate (22.25 g, 53.4 mmol, 95% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.61 (2H, d), 7.45 (2H, d), 4.79 (1H, m), 4.15 (2H, m), 2.88 (1H, m), 2.75 (1H, m), 2.60 (1H, dd), 2.48 (1H, m), 2.40 (1H, dd), 2.33 (1H, tt), 2.12 (1H, tt), 1.90 (1H, m), 1.68 (1H, dt), 1.52 (1H, m), 1.48 (1H, m), 1.27 (3H, t), 0.89 (9H, s), 0.08 (3H, s), −0.07 (3H, s).

Workup

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

Sources & evidence

ORD record
ord-b12c30456e3e4060892e69fcb83cd394
Source dataset
uspto-grants-2013_03
Patent number
US08399451B2

Reaction notes

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