Triphenylphosphine → methyl 5-chloro-2-methyl-3-((tetrahydro-2H-pyran-4-yl)oxy)benzoate

HRID 1050449Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([OH:13])[C:5]([CH3:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[O:14]1[CH2:19][CH2:18][CH:17](O)[CH2:16][CH2:15]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([O:13][CH:17]2[CH2:18][CH2:19][O:14][CH2:15][CH2:16]2)[C:5]([CH3:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8]

Participants

Conditions

Temperature: 55 °C

Procedure

A 100 mL round bottom flask was charged with methyl 5-chloro-3-hydroxy-2-methylbenzoate (500 mg, 2.492 mmol), tetrahydro-2H-pyran-4-ol (318 mg, 3.12 mmol), triphenylphosphine (1307 mg, 4.98 mmol) and tetrahydrofuran (20 mL). The reaction was maintained for 15 min, at which time DIAD (1.454 mL, 7.48 mmol) was added in one portion. The resulting solution was heated at 55° C. for 24 h and then concentrated in vacuo. Purification of the residue by column chromatography (10-50% EtOAc/hexanes) gave methyl 5-chloro-2-methyl-3-((tetrahydro-2H-pyran-4-yl)oxy)benzoate as an orange-oil, which was used directly in the next step. 1H NMR (400 MHz, CHLOROFORM-d) δ 7.42 (d, J=2.02 Hz, 1H), 6.98 (d, J=2.02 Hz, 1H), 4.51 (tt, J=3.73, 7.39 Hz, 1H), 3.99 (ddd, J=3.66, 7.01, 11.31Hz, 2H), 3.91 (s, 3H), 3.64 (ddd, J=3.28, 7.77, 11.43 Hz, 2H), 2.38-2.45 (m, 3H), 1.99-2.10 (m, 2H), 1.74-1.92 (m, 2H). MS(ES) [M+H]+ 285.0

Workup

additionwas added in one portion
concentrationconcentrated in vacuo
customPurification of the residue by column chromatography (10-50% EtOAc/hexanes)

Sources & evidence

ORD record: ord-acf460f153cb43289fb06e7d4cc5ffb3
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09382234B2

Reaction notes

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