1,2-Dichloroethane → HCID 59444220, compound

HRID 1888124Notes

Reaction equation

HRID 1888124 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]2([OH:16])[CH2:13][CH2:12][NH:11][CH2:10][C:9]2([CH3:15])[CH3:14])=[CH:4][CH:3]=1.[CH3:17][CH:18]([CH3:34])[C@@H:19]([CH2:23][NH:24][C:25]([O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])=[O:26])[C:20](O)=[O:21].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]2([OH:16])[CH2:13][CH2:12][N:11]([C:20]([C@@H:19]([CH:18]([CH3:34])[CH3:17])[CH2:23][NH:24][C:25](=[O:26])[O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])=[O:21])[CH2:10][C:9]2([CH3:14])[CH3:15])=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 18437142(S)-4-(4-chlorophenyl)-3,3-dimethylpiperidin-4-olHCID 59444214HCID 59444214, compound

Product 1

HCID 59444220HCID 59444220, compoundYield 58.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-4-(4-chlorophenyl)-3,3-dimethylpiperidin-4-ol (91 mg, 0.38 mmol), (S)-3-methyl-2-(((2-(trimethylsilyl)ethoxy)carbonylamino)methyl)butanoic acid (105 mg, 0.380 mmol), EDC (146 mg, 0.760 mmol) and HOBT (11.64 mg, 0.076 mmol) in CH2Cl2 (2 mL) was added Hunig's Base (0.199 mL, 1.140 mmol). Upon completion of addition, the reaction mixture was stirred at room temperature for 16 hrs. After this time, the reaction mixture was quenched with sat'd NaHCO3 and the crude product was extracted with EtOAc and the extract was washed with brine. The combined aqueous layers were back extracted with EtOAc. The EtOAc extracts were combined, dried over Na2SO4 and evaporated to give a solid residue. The solid residue was purified by Combiflash chromatography (40 g silica gel) eluting with 1:1 and 8:2 EtOAc-hexane to give 110.5 mg of the title compound as a white foamy solid. MS (ESI+)=497.15 (M+H)+.

Workup

  1. additionUpon completion of addition
  2. customAfter this time, the reaction mixture was quenched with sat'd NaHCO3
  3. extractionthe crude product was extracted with EtOAc
  4. washthe extract was washed with brine
  5. extractionThe combined aqueous layers were back extracted with EtOAc
  6. dry with materialdried over Na2SO4
  7. customevaporated
  8. customto give a solid residue
  9. customThe solid residue was purified by Combiflash chromatography (40 g silica gel)
  10. washeluting with 1:1 and 8:2 EtOAc-hexane

Sources & evidence

ORD record
ord-1ab5cee2f0374d5ea69d89c718cb5f9b
Source dataset
uspto-grants-2013_08
Patent number
US08501782B2

Reaction notes

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