Dimethylformamide → 2-(Hydroxymethyl)-2,3-dihydro-1H-indene-5-carbonitrile

HRID 1466039Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][CH:6]([CH2:11][OH:12])[CH2:5]2.[CH3:13][N:14](C=O)C>[C-]#N.[C-]#N.[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:12][CH2:11][CH:6]1[CH2:5][C:4]2[C:8](=[CH:9][CH:10]=[C:2]([C:13]#[N:14])[CH:3]=2)[CH2:7]1

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of (5-Bromo-2,3-dihydro-1H-inden-2-yl)methanol (10 g, 44 mmol), Zn(CN)2 (10.3 g, 88 mmol) and Pd(PPh3)4 (1 g, 0.88 mmol) in 100 mL of DMF was heated at 100-120° C. under N2 atmosphere overnight. Most of the solvent was concentrated and the residue was partitioned between water (100 mL) and EtOAc (100 mL) and separated. The aqueous layer was extracted with EtOAc (50 mL×2). The combined organic layers were washed with brine (200 mL), dried over Na2SO4 and concentrated to dryness. The residue was purified with column chromatography (EtOAc/PE=1:20) to give the title compound. 1H-NMR (400 MHz, CDCl3) δ 7.45 (s, 1H), 7.41 (d, J=7.6 Hz, 1H), 7.27 (d, J=8.0 Hz, 1H), 3.64 (d, J=6.6 Hz, 2H), 3.05-3.13 (m, 2H), 2.70-2.84 (m, 3H).

Workup

concentrationMost of the solvent was concentrated
customthe residue was partitioned between water (100 mL) and EtOAc (100 mL)
customseparated
extractionThe aqueous layer was extracted with EtOAc (50 mL×2)
washThe combined organic layers were washed with brine (200 mL)
dry with materialdried over Na2SO4
concentrationconcentrated to dryness
customThe residue was purified with column chromatography (EtOAc/PE=1:20)

Sources & evidence

ORD record: ord-badcbf6fedf94e698f285b18c23b2583
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08999990B2

Reaction notes

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