Hydrochloric Acid → HCID 66604698, compound

HRID 468690Notes

Reaction equation

[CH2:1]([O:5][C:6]1[CH:7]=[C:8]([CH:11]=[CH:12][C:13]=1[O:14][CH:15]([F:17])[F:16])[CH:9]=O)[C:2]#[C:3][CH3:4].C(O)(=O)[CH2:19][C:20]([OH:22])=[O:21].Cl>N1CCCCC1.N1C=CC=CC=1>[CH2:1]([O:5][C:6]1[CH:7]=[C:8](/[CH:9]=[CH:19]/[C:20]([OH:22])=[O:21])[CH:11]=[CH:12][C:13]=1[O:14][CH:15]([F:17])[F:16])[C:2]#[C:3][CH3:4]

Participants

Conditions

Temperature: 120 °C

Procedure

A solution of 3-(but-2-ynyloxy)-4-difluoromethoxybenzaldehyde (0.53 g, 2.2 mmol) and malonic acid (0.34 g, 3.3 mmol) in a mixture of piperidine (0.2 mL) and pyridine (5.0 mL) was heated to 120° C. and stirred for 16 h. The mixture was cooled to rt and acidified with 1 M HCl. The crude product was collected by filtration and recrystallised from acetonitrile to give (E)-3-(3-(but-2-ynyloxy)-4-difluoromethoxyphenyl)-2-propenoic acid (0.38 g, 61%) as a colourless crystalline solid; mp 206-208° C.; δH (500 MHz, DMSO-d6) 1.84 (t, J=2.2 Hz, 3H, C≡CH3), 4.87 (q, J=2.2 Hz, 2H, OCH2), 6.55 (d, J=16.0 Hz, 1H, CH═CHCO2H), 7.13 (t, J=72.0 Hz, 1H, CHF2), 7.19 (d, J5,6=8.0 Hz, 1H, H5), 7.30 (dd, J5,6=8.0, J2,6=2.0 Hz, 1H, H6), 7.52 (d, J2,6=2.0 Hz, 1H, H2), 7.54 (d, J=16.0 Hz, 1H, CH═CHCO2H), 12.41 (br s, 1H, CO2H); δC (125 MHz, DMSO-d6) 3.1, 56.8, 74.1, 84.1, 113.6, 116.4 (t, J=256 Hz), 119.7, 120.6, 122.0, 132.4, 141.2, 142.9, 148.6, 167.4; νmax 1011, 1113, 1267, 1516, 1629, 1686, 2578, 2924 cm−1.

Workup

temperatureThe mixture was cooled to rt
filtrationThe crude product was collected by filtration
customrecrystallised from acetonitrile

Sources & evidence

ORD record: ord-4c78f0752f064fb3b821371a287066c5
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08624056B2

Reaction notes

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