Propargyl alcohol → N-(2-(3-hydroxyprop-1-ynyl)-4-methylphenyl)-6-(trifluoromethoxy)-3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxamide

HRID 383429Notes

Reaction equation

[CH2:1]([OH:4])[C:2]#[CH:3].Br[C:6]1[CH:11]=[C:10]([CH3:12])[CH:9]=[CH:8][C:7]=1[NH:13][C:14]([CH:16]1[CH2:21][NH:20][C:19]2[CH:22]=[C:23]([O:26][C:27]([F:30])([F:29])[F:28])[CH:24]=[CH:25][C:18]=2[O:17]1)=[O:15].C(N(CC)CC)C>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[OH:4][CH2:1][C:2]#[C:3][C:6]1[CH:11]=[C:10]([CH3:12])[CH:9]=[CH:8][C:7]=1[NH:13][C:14]([CH:16]1[O:17][C:18]2[CH:25]=[CH:24][C:23]([O:26][C:27]([F:30])([F:28])[F:29])=[CH:22][C:19]=2[NH:20][CH2:21]1)=[O:15]

Participants

Conditions

Temperature: 75 °C

Procedure

Prop-2-yn-1-ol (195 mg, 202 μL, 3.48 mmol), N-(2-bromo-4-methyl-phenyl)-6-(trifluoromethoxy)-3,4-dihydro-2H-1,4-benzoxazine-2-carboxamide (300 mg, 0.69 mmol), PdCl2(PPh3)2 (122 mg, 0.17 mmol), CuI (19.88 mg, 0.10 mmol), and triethylamine (970 μL, 6.96 mmol) were combined in DMF (5 mL) and heated at 75° C. for 18 h. Purification by silica gel chromatography (0-50% ethyl acetate/hexanes) provided N-(2-(3-hydroxyprop-1-ynyl)-4-methylphenyl)-6-(trifluoromethoxy)-3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxamide (204 mg, 72% yield). LC/MS m/z 407.4 [M+H]+.

Workup

customPurification by silica gel chromatography (0-50% ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-e205b6dab3454bae8fdd7f25bd3bb94d
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08367660B2

Reaction notes

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