Lactonitrile → (+/-)-2-(Benzo[1,3]dioxol-5-yloxy)-N-[4-(1-cyano-ethoxy)-2-fluoro-benzyl]-nicotinamide

HRID 350992

Reaction equation

HRID 350992 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([O:10][C:11]3[N:28]=[CH:27][CH:26]=[CH:25][C:12]=3[C:13]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][C:18]=3[F:24])=[O:14])=[CH:9][C:4]=2[O:3][CH2:2]1.[C:29](#[N:33])[CH:30]([CH3:32])O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1.C(OCC)(=O)C>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([O:10][C:11]3[N:28]=[CH:27][CH:26]=[CH:25][C:12]=3[C:13]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][CH:30]([C:29]#[N:33])[CH3:32])=[CH:19][C:18]=3[F:24])=[O:14])=[CH:9][C:4]=2[O:3][CH2:2]1

Participants

7

Reactant 4

HCID 6572LactonitrileHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 226101182-(Benzo[1,3]dioxol-5-yloxy)-N-(2-fluoro-4-hydroxy-benzyl)-nicotinamide

Product 1

HCID 22610152(+/-)-2-(Benzo[1,3]dioxol-5-yloxy)-N-[4-(1-cyano-ethoxy)-2-fluoro-benzyl]-nicotinamideYield 26.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 2-(benzo[1,3]dioxol-5-yloxy)-N-(2-fluoro-4-hydroxy-benzyl)-nicotinamide (5 g, 13.1 mmol), (+/−)-lactonitrile (0.93 g, 13.1 mmol) and triphenylphosphine (3.78 g, 14.4 mmol) in tetrahydrofuran (200 mL) at room temperature, diethyl azodicarboxylate (2.3 mL, 14.4 mmol) was added dropwise with stirring. The mixture was stirred at room temperature overnight. Solvents were stripped in vacuo, diluted with ethyl acetate and washed with dilute aqueous sodium hydroxide, brine, and dried (MgSO4). Solvents were stripped in vacuo. The resulting oil was washed with diethyl ether and the precipitate was filtered off. The mother liquor was purified by flash column chromatography (35% ethyl acetate/hexane), affording 1.5 g white solid (26% yield).

Workup

  1. stirringThe mixture was stirred at room temperature overnight
  2. washwashed with dilute aqueous sodium hydroxide, brine
  3. dry with materialdried (MgSO4)
  4. washThe resulting oil was washed with diethyl ether
  5. filtrationthe precipitate was filtered off
  6. customThe mother liquor was purified by flash column chromatography (35% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-0213430e9d804796bfc8823eaf7d4c86
Source dataset
uspto-grants-2007_02
Patent number
US07183293B2

Linked notes

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