1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → 4-(6-fluoro-2H-benzo[b][1,4]oxazin-4(3 H)-yl)-3-methoxybenzonitrile

HRID 528609ノート

反応式

HRID 528609 の反応式
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][CH2:8][NH:7][C:6]=2[CH:11]=1.Br[C:13]1[CH:20]=[CH:19][C:16]([C:17]#[N:18])=[CH:15][C:14]=1[O:21][CH3:22].CC(C)([O-])C.[Na+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.BrC1N=C(N(CC2C=CC(OC)=CC=2)S(C2C=CC3N(C4C=CC(C(F)(F)F)=CC=4Cl)CCOC=3C=2)(=O)=O)SN=1>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][CH2:8][N:7]([C:13]3[CH:20]=[CH:19][C:16]([C:17]#[N:18])=[CH:15][C:14]=3[O:21][CH3:22])[C:6]=2[CH:11]=1

参加物

7

反応物 5

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 162444596-Fluoro-3,4-dihydro-2H-1,4-benzoxazineHCID 225911814-Bromo-3-methoxybenzonitrileHCID 23676156Sodium t-butoxideHCID 89761781N-(3-bromo-1,2,4-thiadiazol-5-yl)-4-(2-chloro-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

生成物 1

HCID 897619874-(6-fluoro-2H-benzo[b][1,4]oxazin-4(3 H)-yl)-3-methoxybenzonitrile収率 92%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

実験手順

To a 10-20 ml microwave vial charged with 6-fluoro-3,4-dihydro-2h-benzo[1,4]oxazine (Ark Pharm) (0.150 g, 0.979 mmol), 4-bromo-3-methoxybenzonitrile (Combi-Blocks) (0.312 g, 1.469 mmol), and sodium t-butoxide (0.240 ml, 1.959 mmol) was added Toluene (9.79 ml). The mixture was purged with argon prior to the additions of xantphos (0.113 g, 0.196 mmol) and tris(dibenzylideneacetone)dipalladium (0) (0.090 g, 0.098 mmol). The mixture was irradiated at 110° C. for 30 min. The resulting dark suspension was filtered through celite and the filtrate dried under reduced pressure and purified with a 50 g SNAP column ramping EtOAc in heptane (0-40%, 10% DCM throughout) providing product as a light brown foam 4-(6-fluoro-2H-benzo[b][1,4]oxazin-4(3 H)-yl)-3-methoxybenzonitrile (0.255 g, 0.897 mmol, 92% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.58-3.65 (m, 2 H) 4.19-4.26 (m, 2 H) 6.07 (dd, J=10.95, 2.93 Hz, 1 H) 6.47 (td, J=8.51, 2.93 Hz, 1 H) 6.79 (dd, J=8.80, 5.58 Hz, 1 H) 7.41-7.45 (m, 1 H) 7.45-7.51 (m, 1 H) 7.62 (d, J=1.66 Hz, 1 H). m/z (ESI) 285.2 (M+H)+.

後処理

  1. customThe mixture was purged with argon
  2. customThe mixture was irradiated at 110° C. for 30 min
  3. filtrationThe resulting dark suspension was filtered through celite
  4. customthe filtrate dried under reduced pressure
  5. custompurified with a 50 g SNAP column

出典と根拠

ORDレコード
ord-a828e27264804483be3e688218d740e9
出典データセット
uspto-grants-2016_05
特許番号
US09346798B2

反応ノート

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