Allyl Alcohol → 3-(2-(Methylthio)benzo[d]thiazol-6-yl)propanal

HRID 1848111Notes

Reaction equation

I[C:2]1[CH:12]=[CH:11][C:5]2[N:6]=[C:7]([S:9][CH3:10])[S:8][C:4]=2[CH:3]=1.[CH2:13]([OH:16])[CH:14]=[CH2:15].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C([O-])(O)=O.[Na+]>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].O>[CH3:10][S:9][C:7]1[S:8][C:4]2[CH:3]=[C:2]([CH2:15][CH2:14][CH:13]=[O:16])[CH:12]=[CH:11][C:5]=2[N:6]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 6-iodo-2-(methylthio)benzo[d]thiazole (5.0 g, 16.3 mmol), allyl alcohol (2.2 mL, 32.6 mmol), Pd(OAc)2 (0.36 g, 1.63 mmol), tris(o-tolyl) phosphine (1.0 g, 3.3 mmol) and NaHCO3 (2.8 g, 32.6 mmol) in DMF (75 mL) was stirred at 100° C. under nitrogen atmosphere for 4 h. Then the mixture was cooled to rt and water (300 mL) was added. The mixture was extracted with EtOAc (200 mL×3). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 10:1 to 5:1 petroleum ether/EtOAc to afford 3-(2-(methylthio)benzo[d]thiazol-6-yl)propanal as a dark yellow oil (2.0 g, 52%). 1H NMR (300 MHz, CDCl3) δ 9.83 (t, J=1.2 Hz, 1H), 7.78 (d, J=8.4 Hz, 1H), 7.58 (d, J=1.2 Hz, 1H), 7.23 (dd, J=1.8, 8.4 Hz, 1H), 3.05 (t, J=7.5 Hz, 2H), 2.85 (t, J=7.5 Hz, 2H), 2.78 (s, 3H). LCMS (ESI) m/z 238 (M+H)+.

Workup

temperatureThen the mixture was cooled to rt
extractionThe mixture was extracted with EtOAc (200 mL×3)
washThe combined organic layers were washed with brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe residue was purified by silica gel chromatography
washeluting with 10:1 to 5:1 petroleum ether/EtOAc

Sources & evidence

ORD record: ord-c61fd1d879854da586453d4f1bcd62c3
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08952058B2

Reaction notes

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