Acetone → 1-Chloro-4-methyl-6-(prop-2-ynyloxy)phthalazine

HRID 1471353Notes

Reaction equation

[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([OH:12])=[CH:9][CH:10]=2)[C:5]([CH3:13])=[N:4][N:3]=1.[CH2:14](Br)[C:15]#[CH:16].C([O-])([O-])=O.[K+].[K+].CC(C)=O>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:12][CH2:16][C:15]#[CH:14])=[CH:9][CH:10]=2)[C:5]([CH3:13])=[N:4][N:3]=1

Participants

Conditions

Temperature: 68 °C

Procedure

The mixture of 1-chloro-6-hydroxy-4-methylphthalazine (8) (195 mg, 1.00 mmol), 80% propargyl bromide (1.30 mmol) in toluene (145 μL), K2CO3 (187 mg, 1.35 mmol), and acetone (8 mL) is stirred at 68° C. under argon for 23 h, and then cooled to room temperature. The mixture is concentrated, diluted with H2O (40 mL), and extracted with ethyl acetate (70 mL and 60 mL). The extract is washed (brine) and dried. After solvent removal at reduced pressure, the residue is purified on silica gel (33% to 56% ethyl acetate/hexane) to give 102 mg (44%) of 11 as alight-yellow solid, mp 178-180° C. IR 2946, 1615, 1378, 1234 cm−1; 1H NMR (DMSO-d6) δ 2.61 (t, J=2.1 Hz, 1H, CH≡C), 2.93 (s, 3H, CH3), 4.91 (d, J=2.1 Hz, 1H, CH≡CCH2), 7.40 (d, J=2.4 Hz, 1H, 5-PhthH), 7.58 (dd, J=9.1, 2.4 Hz, 1H, 7-PhthH), 8.23 ppm (d, J=9.1 Hz, 1H, 8-PhthH).

Workup

temperaturecooled to room temperature
concentrationThe mixture is concentrated
additiondiluted with H2O (40 mL)
extractionextracted with ethyl acetate (70 mL and 60 mL)
washThe extract is washed (brine)
customdried
customAfter solvent removal at reduced pressure
customthe residue is purified on silica gel (33% to 56% ethyl acetate/hexane)

Sources & evidence

ORD record: ord-ec2d350396b34f3db892b2ce63d61d86
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09012217B2

Reaction notes

Loading…