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 528609Notes

Reaction equation

HRID 528609 reaction equation
[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

Participants

7

Reactant 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 89761781HCID 89761781, compound

Product 1

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

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-a828e27264804483be3e688218d740e9
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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