Picolyl chloride hydrochloride → HCID 66932235, compound

HRID 2046726Notes

Reaction equation

HRID 2046726 reaction equation
[CH3:1][O:2][C:3](=[O:29])/[CH:4]=[CH:5]/[C:6]1[CH:7]=[C:8]2[C:25](=[CH:26][CH:27]=1)[O:24][C:11]1([CH2:16][CH2:15][N:14]([C:17](OC(C)(C)C)=O)[CH2:13][CH2:12]1)[CH2:10][C:9]2=[O:28].Cl.ClC[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=1>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:29])/[CH:4]=[CH:5]/[C:6]1[CH:7]=[C:8]2[C:25](=[CH:26][CH:27]=1)[O:24][C:11]1([CH2:12][CH2:13][N:14]([CH2:17][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=3)[CH2:15][CH2:16]1)[CH2:10][C:9]2=[O:28]

Participants

4

Reactant 2

HCID 23392Picolyl chloride hydrochlorideHCID 52952087(E)-3-{1'-tert-butoxycarbonyl-4-oxo-spiro[chromane-2,4'-piperidine]-6-yl}-acrylic acid methyl ester2×

Product 1

HCID 66932235HCID 66932235, compoundYield 78.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A suspension of (E)-3-{4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester hydrochloride (150 mg, 0.44 mmol, Intermediate 1) in DCM (7 ml) was treated with TEA (0.49 ml, 3.52 mmol) and 2-(chloromethyl)pyridine hydrochloride (145 mg, 0.89 mmol), and stirred at RT for 48 h. Catalytic amount of KI was added and the reaction was stirred at RT overnight. The mixture was then washed with water and brine, dried and concentrated. The crude residue was purified by column chromatography (eluent: DCM/MeOH/NH4OH 96:4:0.2) to give (E)-3-{1′-(pyridin-2-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester (136 mg).

Workup

  1. additionCatalytic amount of KI was added
  2. stirringthe reaction was stirred at RT overnight
  3. washThe mixture was then washed with water and brine
  4. customdried
  5. concentrationconcentrated
  6. customThe crude residue was purified by column chromatography (eluent: DCM/MeOH/NH4OH 96:4:0.2)

Sources & evidence

ORD record
ord-60291cc90d3e46be82958dbae0959797
Source dataset
uspto-grants-2013_11
Patent number
US08592444B2

Reaction notes

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