Potassium Carbonate → (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

HRID 1481970Notes

Reaction equation

HRID 1481970 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:26](=[O:31])[C:27]([O:29][CH3:30])=[O:28])[CH2:7][CH2:6]1)[CH2:2][CH:3]=[CH2:4].CC(O)C.C(=O)=O.[B]1OC2C(=CC=CC=2)O1.C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1>[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]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 6327445BenzcatechinboraneHCID 86586944Isopropanol carbon dioxideHCID 118308840Ethyl 5-(4-(but-3-en-1-yl)-4-methylpiperidin-1-yl)-6-(2-methoxy-2-oxoacetyl)-7-methylimidazo[1,2-a]pyridine-2-carboxylate

Product 1

HCID 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-carboxylateYield 115%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

A solution of ethyl 5-(4-(but-3-en-1-yl)-4-methylpiperidin-1-yl)-6-(2-methoxy-2-oxoacetyl)-7-methylimidazo[1,2-a]pyridine-2-carboxylate (0.44 g, 1.00 mmol, 1 equiv) and R-5,5-diphenyl-2-methyl-3,4-propano-1,3,2-oxazaborlidine (1.59 mL of a 1 M solution in toluene, 1.59 mmol, 1.6 equiv) in toluene (10 mL) was cooled to −30° C. (IPA/dry ice). Catecholborane (0.34 mL, 1.59 mmol, 1.6 equiv) was added and the reaction was stirred at −15° C.-30° C. for 3 h. The reaction was then added to 10% K2CO3 and extracted with ether (×3). The combined ether extracts were dried (MgSO4) and concentrated in vacuo. The crude product was purified by flash column chromatography (30-100% EtOAc/hex) to provide the product (0.51 g, ˜100%) as a viscous colorless oil. NMR shows contamination with a CBS byproduct accounting for extra mass. 1H NMR (500 MHz, CDCl3) δ 8.26 (s, 1H), 7.40 (s, 1H), 5.98-5.84 (m, 1H), 5.61 (d, J=11.0 Hz, 1H), 5.17-4.98 (m, 2H), 4.55-4.46 (m, 2H), 3.81 (s, 3H), 3.61 (t, J=10.9 Hz, 2H), 3.11-2.94 (m, 4H), 2.44 (d, J=0.9 Hz, 3H), 2.18-2.09 (m, 2H), 1.82-1.53 (m, 4H), 1.50-1.44 (m, 3H), 1.16 (s, 3H); LCMS (ESI, M+1): 444.25.

Workup

  1. extractionextracted with ether (×3)
  2. dry with materialThe combined ether extracts were dried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by flash column chromatography (30-100% EtOAc/hex)

Sources & evidence

ORD record
ord-6d0e890664bb49fd9d6139b76b24ba9a
Source dataset
uspto-grants-2016_08
Patent number
US09409922B2

Reaction notes

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