Diisopropylethylamine → HCID 86716011, compound

HRID 1482498Notes

Reaction equation

HRID 1482498 reaction equation
[F:1][C:2]([C:5]1[N:10]=[CH:9][C:8]([CH:11]=O)=[CH:7][N:6]=1)([F:4])[CH3:3].[Si]([C:17]#[N:18])(C)(C)C.Cl.[F:20][C:21]1([F:27])[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1.CCN(C(C)C)C(C)C>C1COCC1.[I-].[Zn+2].[I-]>[F:1][C:2]([C:5]1[N:10]=[CH:9][C:8]([CH:11]([N:24]2[CH2:25][CH2:26][C:21]([F:27])([F:20])[CH2:22][CH2:23]2)[C:17]#[N:18])=[CH:7][N:6]=1)([F:4])[CH3:3]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 82115Trimethylsilyl cyanideHCID 27583514,4-Difluoropiperidine hydrochlorideHCID 86716010HCID 86716010, compound

Product 1

HCID 86716011HCID 86716011, compoundYield 24%

Reagents, catalysts & solvents 2

HCID 9883512zinc(II)iodideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-(1,1-difluoroethyl)pyrimidine-5-carbaldehyde (166 mg, 0.270 mmol, 28%) in THF (4 ml) was added TMS cyanide (79 mg, 0.1 ml, 0.8 mmol) and zinc iodide (2.2 mg, 6.89 μmol). The mixture was stirred for 15 min. To the mixture was added 4,4-difluoropiperidine hydrochloride (62 mg, 0.393 mmol) and DIPEA (37 mg, 0.05 ml, 0.286 mmol). The resultant mixture was stirred at room temperature overnight. The volatiles were removed by rotary evaporator and the reaction was purified by column chromatography on silica gel (petroleum ether: EtOAc=1:0 to 0:1) to afford 2-(2-(1,1-difluoroethyl)pyrimidin-5-yl)-2-(4,4-difluoropiperidin-1-yl)acetonitrile (as a 1:1 mixture of nitrile and aldehyde) (39 mg, 24% yield). 1H NMR (CDCl3 500 MHz): δ 9.03 (s, 2H), 5.02 (s, 1H), 2.75 (m, 4H), 2.10 (m, 6H).

Workup

  1. customThe volatiles were removed by rotary evaporator
  2. customthe reaction was purified by column chromatography on silica gel (petroleum ether: EtOAc=1:0 to 0:1)

Sources & evidence

ORD record
ord-65e4ee6ca58b41fa8673bb3fb659a58b
Source dataset
uspto-grants-2016_08
Patent number
US09415055B2

Reaction notes

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