Acetic acid, (2-iodophenoxy)-, ethyl ester → N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)-2-(2-iodophenoxy)acetamide

HRID 2202657Notes

Reaction equation

[I:1][C:2]1[CH:14]=[CH:13][CH:12]=[CH:11][C:3]=1[O:4][CH2:5][C:6]([O:8]CC)=O.[NH2:15][CH2:16][CH:17]([OH:29])[CH2:18][N:19]1[CH2:28][CH2:27][C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:20]1>CCO>[CH2:20]1[C:21]2[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:27][CH2:28][N:19]1[CH2:18][CH:17]([OH:29])[CH2:16][NH:15][C:6](=[O:8])[CH2:5][O:4][C:3]1[CH:11]=[CH:12][CH:13]=[CH:14][C:2]=1[I:1]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of ethyl 2-(2-iodophenoxy)acetate (900 mg, 2.94 mmol) in EtOH (3 mL) was added 1-amino-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-ol (677 mg, 3.24 mmol). The reaction mixture was heated under microwave conditions at 80° C. for 3 h, cooled and concentrated. The crude product was used in the next step without further purification. (1.3 g, yield 95%) MS (ESI+) e/z: 467.1 [M+1]+. 1H NMR (MeOD, 400 MHz), δ ppm: 7.80 (dd, J=1.0, 7.8 Hz, 1H), 7.41-7.30 (m, 1H), 7.15-7.05 (m, 3H), 7.05-6.99 (m, 1H), 6.96 (d, J=8.0 Hz, 1H), 6.87-6.76 (m, 1H), 4.66-4.53 (m, 2H), 4.06 (quin, J=5.9 Hz, 1H), 3.77-3.63 (m, 2H), 3.58 (dd, J=4.5, 13.6 Hz, 1H), 3.38 (dd, J=6.4, 13.7 Hz, 1H), 2.98-2.86 (m, 2H), 2.86-2.76 (m, 2H), 2.66-2.57 (m, 2H).

Workup

temperaturecooled
concentrationconcentrated
customThe crude product was used in the next step without further purification

Sources & evidence

ORD record: ord-42da9fad9f4642a58527768ebd5b6689
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09365555B2

Reaction notes

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