Dichloromethane → (S)-ethyl 5-(4-(but-3-en-1-yl)-4-methylpiperidin-1-yl)-6-(1-(tert-butoxy)-2-methoxy-2-oxoethyl)-7-methylimidazo[1,2-a]pyridine-2-carboxylate

HRID 1481971Notes

Reaction equation

HRID 1481971 reaction equation
[CH2:1]([C:5]1([CH3:32])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[CH:17]=[C:18]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[N:19]=[C:15]3[CH:14]=[C:13]([CH3:25])[C:12]=2[C@H:26]([OH:31])[C:27]([O:29][CH3:30])=[O:28])[CH2:7][CH2:6]1)[CH2:2][CH:3]=[CH2:4].C(Cl)Cl.C([O-])(O)=O.[Na+]>C(OC(C)=O)(C)(C)C>[CH2:1]([C:5]1([CH3:32])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[CH:17]=[C:18]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[N:19]=[C:15]3[CH:14]=[C:13]([CH3:25])[C:12]=2[C@H:26]([O:31][C:5]([CH3:10])([CH3:6])[CH3:1])[C:27]([O:29][CH3:30])=[O:28])[CH2:7][CH2:6]1)[CH2:2][CH:3]=[CH2:4]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 118319909(S)-ethyl 5-(4-(but-3-en-1-yl)-4-methylpiperidin-1-yl)-6-(1-hydroxy-2-methoxy-2-oxoethyl)-7-methylimidazo[1,2-a]pyridine-2-carboxylate

Product 1

HCID 118319913(S)-ethyl 5-(4-(but-3-en-1-yl)-4-methylpiperidin-1-yl)-6-(1-(tert-butoxy)-2-methoxy-2-oxoethyl)-7-methylimidazo[1,2-a]pyridine-2-carboxylateYield 56.8%

Reagents, catalysts & solvents 1

HCID 10908tert-Butyl acetateSolvent

Procedure

To a solution of (S)-ethyl 5-(4-(but-3-en-1-yl)-4-methylpiperidin-1-yl)-6-(1-hydroxy-2-methoxy-2-oxoethyl)-7-methylimidazo[1,2-a]pyridine-2-carboxylate (0.50 g, 1.13 mmolo, 1 equiv) in t-BuOAc (18 mL) was added 70% HClO4 (0.48 mL, 5.64 mmol, 5 equiv). A white precipitate formed. DCM (5 mL) was added to aid solubility. After 1 h, the reaction was carefully added to saturated aqueous NaHCO3 and extracted with DCM (×3). The combined DCM extracts were dried (Na2SO4) and concentrated in vacuo. The crude product was purified by flash column chromatography (0-100% EtOAc/hex) to provide the product (0.16 g, 28%) as a white foam. In addition, starting material (0.38 g) was recovered. 1H NMR (400 MHz, CDCl3) [note: major rotamer transcribed, 3:2 mixture of rotamers] δ8.23 (s, 1H), 7.33 (s, 1H), 6.06 (s, 1H), 5.97-5.81 (m, 1H), 5.17-4.97 (m, 2H), 4.53-4.42 (m, 2H), 3.71 (s, 3H), 3.69-3.64 (m, 1H), 3.57-3.50 (m, 1H), 3.17-3.07 (m, 1H), 2.88 (d, J=12.0 Hz, 1H), 2.46-2.44 (m, 3H), 2.18-2.08 (m, 2H), 1.71-1.58 (m, 6H), 1.48-1.43 (m, 3H), 1.25 (s, 9H), 1.16 (s, 3H); LCMS (ESI, M+1): 500.35.

Workup

  1. customA white precipitate formed
  2. extractionextracted with DCM (×3)
  3. dry with materialThe combined DCM extracts were dried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by flash column chromatography (0-100% EtOAc/hex)

Sources & evidence

ORD record
ord-240629bfa5ef45a6871895fb3d0e0209
Source dataset
uspto-grants-2016_08
Patent number
US09409922B2

Reaction notes

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