Isopropylamine → Ethyl 2-(isopropylamino)-6-methylisonicotinate

HRID 1908742Notes

Reaction equation

HRID 1908742 reaction equation
[CH2:1]([O:3][C:4](=[O:13])[C:5]1[CH:10]=[C:9]([CH3:11])[N:8]=[C:7](Cl)[CH:6]=1)[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].[CH:20]([NH2:23])([CH3:22])[CH3:21].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1>[CH2:1]([O:3][C:4](=[O:13])[C:5]1[CH:10]=[C:9]([CH3:11])[N:8]=[C:7]([NH:23][CH:20]([CH3:22])[CH3:21])[CH:6]=1)[CH3:2]

Participants

6

Reactant 4

HCID 6363IsopropylamineHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 22625009Ethyl 2-Chloro-6-methylisonicotinate

Product 1

HCID 59504215Ethyl 2-(isopropylamino)-6-methylisonicotinateYield 67.7%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of 2-chloro-6-methyl-isonicotinic acid ethyl ester (5.20 g, 26.0 mmol) in dioxane (200 mL), Cs2CO3 (25.5 g, 78.1 mmol) and isopropylamine (9.24 g, 156.3 mmol) is added. The mixture is degassed and put under N2 before Xantphos (5.43 g, 9.38 mmol) and Pd(II) acetate (1.17 g, 5.26 mmol) are added. The mixture is stirred in a sealed vessel at 85° C. for 18 h. The mixture is cooled to rt, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 7:3 to give 2-isopropylamino-6-methyl-isonicotinic acid ethyl ester (3.91 g) as an orange solid; LC-MS: tR=0.67 min; [M+1]+=223.10.

Workup

  1. customThe mixture is degassed
  2. additionare added
  3. temperatureThe mixture is cooled to rt
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product is purified by CC on silica gel eluting with heptane:EA 7:3

Sources & evidence

ORD record
ord-191d6945db324f0d99bdb10a34513dd9
Source dataset
uspto-grants-2013_12
Patent number
US08598208B2

Reaction notes

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