N-methyl-2-pyrrolidone → 2-(Morpholin-4-yl)-3-trifluoromethyl-5-cyanopyridine

HRID 1820986Notes

Reaction equation

[N:1]1([C:7]2[C:12]([C:13]([F:16])([F:15])[F:14])=[CH:11][C:10](Br)=[CH:9][N:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[CH3:18][N:19]1CCCC1=O>[C-]#N.[Zn+2].[C-]#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[N:1]1([C:7]2[C:12]([C:13]([F:16])([F:15])[F:14])=[CH:11][C:10]([C:18]#[N:19])=[CH:9][N:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 160 mg (0.63 mmol) of 2-(morpholin-4-yl)-3-trifluoromethyl-5-bromopyridine (from Step C), 117 mg (1.0 mmol) of zinc cyanide, 20.1 mg (0.22 mmol) of tris(dibenzylideneacetone)dipalladium(0) and 48.7 mg (0.088) mmol of 1,1′-bis(diphenylphosphino)ferrocene in 2 mL of N-methylpyrrolidinone under argon was stirred at 100° C. for 1 h. The mixture was cooled and partitioned between ether and water. The organic layer was dried and concentrated. Chromatography on a Biotage 40S cartridge using 9:1 v/v hexanes/ether then 17:3 v/v hexanes/ether as the eluant afforded 87 mg of the title compound: ESI-MS (m/z) 258.2; HPLC A: 3.04 min.

Workup

temperatureThe mixture was cooled
custompartitioned between ether and water
customThe organic layer was dried
concentrationconcentrated

Sources & evidence

ORD record: ord-e8657ee4ac0048c6ac4882b9e1e8d85c
Source dataset: uspto-grants-2009_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07605171B2

Reaction notes

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