Tetrahydrofuran → 3-[2-Methyl-3,4-dihydro-3-oxo-4-(propynyl)-2H-1,4-benzoxazin-6-yl]-6-(trifluoromethyl)-2,4(1H,3H)-pyrimidinedione

HRID 703038

Reaction equation

[H-].[Na+].O1CCCC1.[NH2:8][C:9]([C:16]([F:19])([F:18])[F:17])=[CH:10][C:11]([O:13]CC)=O.[N:20]([C:23]1[CH:24]=[CH:25][C:26]2[O:31][CH:30]([CH3:32])[C:29](=[O:33])[N:28]([CH2:34][C:35]#[CH:36])[C:27]=2[CH:37]=1)=[C:21]=[O:22]>C(O)(=O)C>[CH3:32][CH:30]1[C:29](=[O:33])[N:28]([C:34]#[C:35][CH3:36])[C:27]2[CH:37]=[C:23]([N:20]3[C:11](=[O:13])[CH:10]=[C:9]([C:16]([F:17])([F:18])[F:19])[NH:8][C:21]3=[O:22])[CH:24]=[CH:25][C:26]=2[O:31]1

Participants

Conditions

Temperature: -70 °C

Procedure

A slurry of 1.4 g. of sodium hydride in 25 ml. of dry tetrahydrofuran (THF) was cooled to -10° C. To the cooled and stirred slurry was added a solution of 10.0 g. of ethyl 3-amino-4,4,4-trifluoro-2-butenoate in 50 ml. of THF. The addition of this solution was made over a period of 30 minutes. The resultant light brown reaction mixture was cooled to -70° C. A solution of 13.3 g. of 6-isocyanato-2- methyl-3,4-dihydro-3-oxo-4-(2-propynyl)-2H-1,4-benzoxazine in 75 ml. of THF was added to the chilled reaction mixture over a period of 10 minutes. After stirring at -70° C. for 30 minutes, the temperature was allowed to rise slowly to 10° C. At that point 3.6 ml. of acetic acid was added to the mixture. A beige solid precipitated. 19.0 Grams of the solid was recovered by filtering it from the reaction mixture.

Workup

temperatureTo the cooled
additionwas added a solution of 10.0 g
additionThe addition of this solution
stirringAfter stirring at -70° C. for 30 minutes
customto rise slowly to 10° C
customA beige solid precipitated
custom19.0 Grams of the solid was recovered
filtrationby filtering it from the reaction mixture

Sources & evidence

ORD record: ord-d05d21b41e2b446ba3921ae65d778a14
Source dataset: uspto-grants-1991_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04981508

Linked notes

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