Pyridine → 2-Cyclopentyl-6-methoxy-isonicotinonitrile

HRID 2278770Notes

Reaction equation

HRID 2278770 reaction equation
N1C=CC=CC=1.[CH:7]1([C:12]2[CH:13]=[C:14]([CH:18]=[C:19]([O:21][CH3:22])[N:20]=2)[C:15]([NH2:17])=O)[CH2:11][CH2:10][CH2:9][CH2:8]1.FC(F)(F)C(OC(=O)C(F)(F)F)=O>C(Cl)Cl>[CH:7]1([C:12]2[CH:13]=[C:14]([CH:18]=[C:19]([O:21][CH3:22])[N:20]=2)[C:15]#[N:17])[CH2:8][CH2:9][CH2:10][CH2:11]1

Participants

5

Reactant 3

HCID 1049PyridineHCID 9845Trifluoroacetic anhydrideHCID 674914362-Cyclopentyl-6-methoxy-isonicotinamide

Product 1

HCID 674912332-Cyclopentyl-6-methoxy-isonicotinonitrileYield 68%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Pyridine (8.86 g, 91.3 mmol) is added to a solution of 2-cyclopentyl-6-methoxy-isonicotinamide (3.35 g, 15.2 mmol) in DCM (100 mL). The mixture is cooled to 0° C. before trifluoroacetic acid anhydride (9.58 g, 45.6 mmol) is added portionwise. The mixture is stirred at 0° C. for 1 h before it is diluted with DCM (100 mL) and washed with sat. aq. NaHCO3 solution (100 mL) and brine (100 mL). The separated org. phase is dried over MgSO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 9:1 to give 2-cyclopentyl-6-methoxy-isonicotinonitrile (2.09 g) as a pale yellow oil; LC-MS**: tR=0.80 min, [M+1]+=not detectable; 1H NMR (D6-DMSO): δ 1.61-1.82 (m, 6H), 1.94-2.03 (m, 2H), 3.16 (quint, J=7.8 Hz, 1H), 3.89 (s, 3H), 7.15 (s, 1H), 7.28 (s, 1H).

Workup

  1. additionis added portionwise
  2. washwashed with sat. aq. NaHCO3 solution (100 mL) and brine (100 mL)
  3. dry with materialphase is dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product is purified by CC on silica gel eluting with heptane:EA 9:1

Sources & evidence

ORD record
ord-37cf1f27ae884913a17d42d7a16de1fc
Source dataset
uspto-grants-2015_09
Patent number
US09133179B2

Reaction notes

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