Propionitrile → HCID 57470608, compound

HRID 602061Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][C:3]=1[C@H:9]([OH:12])[CH2:10][OH:11].C(#N)CC.[C:17]([O:21][CH2:22][CH3:23])(=[O:20])[CH:18]=[CH2:19].C(N(CC)CC)C.CC1C(P(C2C(C)=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1>CC([O-])=O.CC([O-])=O.[Pd+2].CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5](/[CH:19]=[CH:18]/[C:17]([O:21][CH2:22][CH3:23])=[O:20])=[CH:4][C:3]=1[C@H:9]([OH:12])[CH2:10][OH:11]

Participants

Conditions

Temperature: 80 °C

Procedure

(1S)-1-(2-chloro-5-iodophenyl)ethane-1,2-diol (2.60 g, 8.71 mmol), propionitrile (87 mL), ethyl acrylate (1.24 mL, 11.32 mmol), and triethylamine (3.6 mL, 26.13 mmol) were combined and N2 was flushed through the solution for 10 minutes. Then Pd(OAc)2 (587 mg, 0.871 mmol) and P(O-tol)3 (1.06 g, 3.48 mmol) were added and the solution was heated to 80° C. After 16 h, the solution was cooled to rt and then EtOAc was added. The solution was washed with 1N HCl (2×), brine, dried, concentrated, and purified by Biotage chromatography (0%-100% EtOAc/hexanes) to afford 1.90 g of product as an oil (81%). 1H NMR (400 MHz, chloroform-d) δ ppm 7.79 (d, J=1.77 Hz, 1 H) 7.65 (d, J=16.17 Hz, 1 H) 7.34-7.40 (m, 2 H) 6.45 (d, J=15.92 Hz, 1 H) 5.24 (ddd, J=7.39, 2.84, 2.65 Hz, 1 H) 4.27 (q, J=7.24 Hz, 2 H) 3.89-3.97 (m, 1 H) 3.57 (ddd, J=11.49, 7.45, 4.55 Hz, 1 H) 2.87 (d, J=3.28 Hz, 1 H) 2.18 (t, J=5.81 Hz, 1 H) 2.05 (s, 3 H) 1.34 (t, J=7.20 Hz, 2 H).

Workup

customN2 was flushed through the solution for 10 minutes
temperaturethe solution was cooled to rt
washThe solution was washed with 1N HCl (2×), brine
customdried
concentrationconcentrated
custompurified by Biotage chromatography (0%-100% EtOAc/hexanes)

Sources & evidence

ORD record: ord-daa56d881f2c41878d0c63df863066a7
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07902394B2

Reaction notes

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