Dimethylacetamide → 4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]benzonitrile

HRID 1468849Notes

Reaction equation

Br[C:2]1[CH:27]=[CH:26][C:5]([CH2:6][O:7][CH2:8][C@@H:9]2[CH2:11][C@@H:10]2[CH:12]2[CH2:17][CH2:16][N:15]([C:18]3[N:23]=[CH:22][C:21]([CH2:24][CH3:25])=[CH:20][N:19]=3)[CH2:14][CH2:13]2)=[CH:4][CH:3]=1.C[C:29]([N:31](C)C)=O>CCOCC.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].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].[C-]#N.[C-]#N.[Zn+2].[Zn]>[CH2:24]([C:21]1[CH:20]=[N:19][C:18]([N:15]2[CH2:16][CH2:17][CH:12]([C@H:10]3[CH2:11][C@H:9]3[CH2:8][O:7][CH2:6][C:5]3[CH:26]=[CH:27][C:2]([C:29]#[N:31])=[CH:3][CH:4]=3)[CH2:13][CH2:14]2)=[N:23][CH:22]=1)[CH3:25]

Participants

Conditions

Temperature: 100 °C

Procedure

The product of example 54 (step A) (500 mg, 1.17 mmol), Pd2(dba)3 (43 mg, 0.046 mmol), dppf (51.5 mg, 0.093 mmol), Zn(CN)2 (89 mg, 0.755 mmol) and zinc dust (18 mg, 0.278 mmol) in DMA (1 mL) was evacuated and back-filled with argon (×3). The mixture was stirred at 100° C. for 4 h. The reaction was cooled to room temperature, diluted with Et2O and filtered through a pad of silica. The filtrate was concentrated under vacuum to leave a residue which was purified by silica gel column chromatography (elution with 5:1 hexane:ethyl acetate) to yield the title compound as a colorless gum. MS (ESI) m/z 377 [M+H]+.

Workup

additionback-filled with argon (×3)
temperatureThe reaction was cooled to room temperature
filtrationfiltered through a pad of silica
concentrationThe filtrate was concentrated under vacuum
customto leave a residue which
customwas purified by silica gel column chromatography (elution with 5:1 hexane:ethyl acetate)

Sources & evidence

ORD record: ord-7766252cd4214ae488dd8d1d329c47ad
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09006228B2

Reaction notes

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