Hydrochloric Acid → 2-(3,4-dichloro-phenyl)-2-hydroxy-N-[2-(3-methoxy-4-pent-2-ynyloxy-phenyl)-ethyl]-acetamide

HRID 992446Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:15][CH2:16][NH:17][CH:18]=[O:19])[CH:6]=[CH:7][C:8]=1[O:9][CH2:10][C:11]#[C:12][CH2:13][CH3:14].C(N(CC)CC)C.C(=O)(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl.[Cl:39][C:40]1[CH:41]=[C:42]([CH:45]=[CH:46][C:47]=1[Cl:48])[CH:43]=[O:44].Cl>C(Cl)Cl.Cl[Ti](Cl)(Cl)Cl>[Cl:39][C:40]1[CH:41]=[C:42]([CH:43]([OH:44])[C:18]([NH:17][CH2:16][CH2:15][C:5]2[CH:6]=[CH:7][C:8]([O:9][CH2:10][C:11]#[C:12][CH2:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=2)=[O:19])[CH:45]=[CH:46][C:47]=1[Cl:48]

Participants

Conditions

Temperature: -78 °C

Procedure

34 g (13.0 mmol) N-[2-(3-methoxy-4-pent-2-ynyloxy-phenyl)-ethyl]-formamide and 4.3 ml (32 mmol) triethylamine are dissolved in 13 ml CH2Cl2. 1.4 g (4.7 mmol) bis(trichloromethyl) carbonate (triphosgene) in 9 ml CH2Cl2 is added at +5° C. The mixture is stirred for 4 hours at +5° C. and then cooled to −78° C. A solution of 1.43 ml (13.0 mmol) TiCl4 in 20 ml CH2Cl2 is added and the mixture is stirred for 2 hours at −40° C. 2.5 g (12.9 mmol) 3,4-dichlorobenzal-dehyde in 7 ml CH2Cl2 is added dropwise and the mixture is stirred for 17 h at room temperature. The mixture is hydrolysed with 7 ml HCl 5N, stirred 30 minutes at room temperature and washed with water. After evaporation the residue is submitted to flash-chromatography (ethyl acetate 6,hexanes 4) to give the 2-(3,4-dichloro-phenyl)-2-hydroxy-N-[2-(3-methoxy-4-pent-2-ynyloxy-phenyl)-ethyl]-acetamide.

Workup

stirringthe mixture is stirred for 2 hours at −40° C
stirringthe mixture is stirred for 17 h at room temperature
stirringstirred 30 minutes at room temperature
washwashed with water
customAfter evaporation the residue

Sources & evidence

ORD record: ord-ccf4ed2f68bd4cdc838f02a87b601bd4
Source dataset: uspto-grants-2002_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06469005B1

Reaction notes

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