Pyridine → HCID 67264998, compound

HRID 1685186Notes

Reaction equation

HRID 1685186 reaction equation
S(Cl)(Cl)=O.[C:5]([O:9][C:10]([N:12]1[CH2:17][CH2:16][CH:15]([C:18]([OH:20])=O)[CH2:14][CH2:13]1)=[O:11])([CH3:8])([CH3:7])[CH3:6].N1C=CC=CC=1.Cl.[CH2:28]([O:35][C:36]([N:38]1[CH2:43][CH2:42][CH2:41][C@@H:40]([NH:44][CH2:45][C:46]([C:48]2[CH:53]=[CH:52][C:51]([F:54])=[C:50]([C:55]([F:58])([F:57])[F:56])[CH:49]=2)=[O:47])[CH2:39]1)=[O:37])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>C(Cl)Cl>[C:5]([O:9][C:10]([N:12]1[CH2:13][CH2:14][CH:15]([C:18](=[O:20])[N:44]([C@@H:40]2[CH2:41][CH2:42][CH2:43][N:38]([C:36]([O:35][CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[O:37])[CH2:39]2)[CH2:45][C:46]([C:48]2[CH:53]=[CH:52][C:51]([F:54])=[C:50]([C:55]([F:56])([F:57])[F:58])[CH:49]=2)=[O:47])[CH2:16][CH2:17]1)=[O:11])([CH3:6])([CH3:7])[CH3:8]

Participants

6

Reactant 4

HCID 1049PyridineHCID 24386Thionyl ChlorideHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 67265031HCID 67265031, compound

Product 1

HCID 67264998HCID 67264998, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Add thionyl chloride (1.2 equiv; 10.5 mmol; 765 μL) dropwise over 3 min at 20° C. to a solution of piperidine-1,4-dicarboxylic acid mono-tert-butyl ester (1.00 equiv; 8.75 mmol; 2.03 g) and pyridine (5 equiv; 43.74 mmol; 3.54 mL) in DCM (60 mL). Stir 90 min. Add (R)-3-[2-(4-fluoro-3-trifluoromethyl-phenyl)-2-oxo-ethylamino]-piperidine-1-carboxylic acid benzyl ester hydrochloride (0.80 equiv; 7.00 mmol; 3.32 g) followed by TEA (3.5 equiv; 30.62 mmol; 4.3 mL) dropwise over 3 min and stir 18 h. Wash the organic phase 3× with 1N HCl, water, brine, dry over MgSO4, filter and evaporate. Purify the residue on 150 g silica gel with 20-50% EA/DCM to provide the title compound (2.86 g; 4.41 mmol; 50%). MS (ES+): m/z=672 (M+Na).

Workup

  1. stirringstir 18 h
  2. washWash the organic phase 3× with 1N HCl, water, brine
  3. dry with materialdry over MgSO4
  4. filtrationfilter
  5. customevaporate
  6. customPurify the residue on 150 g silica gel with 20-50% EA/DCM

Sources & evidence

ORD record
ord-90ce420868094f03bcba125e14005155
Source dataset
uspto-grants-2012_04
Patent number
US08148387B2

Reaction notes

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