1,4-Dioxane → tert-butyl 4-(2-(7-((perfluorophenoxy)sulfonyl)-2H-benzo[b][1,4]oxazin-4(3H)-yl)-5-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 528527Notes

Reaction equation

HRID 528527 reaction equation
Br[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[N:12]1[CH2:17][CH2:16][O:15][C:14]2[CH:18]=[C:19]([S:22]([O:25][C:26]3[C:31]([F:32])=[C:30]([F:33])[C:29]([F:34])=[C:28]([F:35])[C:27]=3[F:36])(=[O:24])=[O:23])[CH:20]=[CH:21][C:13]1=2.CC1(C)C(C)(C)OB([C:45]2[CH2:50][CH2:49][N:48]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:47][CH:46]=2)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>O>[F:36][C:27]1[C:28]([F:35])=[C:29]([F:34])[C:30]([F:33])=[C:31]([F:32])[C:26]=1[O:25][S:22]([C:19]1[CH:20]=[CH:21][C:13]2[N:12]([C:3]3[CH:4]=[CH:5][C:6]([C:8]([F:9])([F:10])[F:11])=[CH:7][C:2]=3[C:45]3[CH2:50][CH2:49][N:48]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:47][CH:46]=3)[CH2:17][CH2:16][O:15][C:14]=2[CH:18]=1)(=[O:23])=[O:24]

Participants

6

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 89761935perfluorophenyl 4-(2-bromo-4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonate

Product 1

HCID 89761263tert-butyl 4-(2-(7-((perfluorophenoxy)sulfonyl)-2H-benzo[b][1,4]oxazin-4(3H)-yl)-5-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylateYield 79.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A vial was charged with perfluorophenyl 4-(2-bromo-4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonate (EXAMPLE 46, STEP 1) (134.9 mg, 0.223 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (104 mg, 0.335 mmol), Pd(AmPhos)2Cl2 (7.90 mg, 0.011 mmol), potassium phosphate (142 mg, 0.670 mmol), dioxane (1116 μL), and water (372 μL). The vial as sealed and heated in a microwave reactor for 1 h at 100° C. The mixture was extracted with EtOAc (3×). The combined organic extracts were concentrated, and the residue was purified by chomatography on silica gel (12 g, 0 to 40% EtOAc/Heptane) to give tert-butyl 4-(2-(7-((perfluorophenoxy)sulfonyl)-2H-benzo[b][1,4]oxazin-4(3H)-yl)-5-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate (125.5 mg, 0.178 mmol) as a clear oil. m/z (ESI) 729.4 (M+H)+.

Workup

  1. customThe vial as sealed
  2. extractionThe mixture was extracted with EtOAc (3×)
  3. concentrationThe combined organic extracts were concentrated
  4. customthe residue was purified by chomatography on silica gel (12 g, 0 to 40% EtOAc/Heptane)

Sources & evidence

ORD record
ord-31f97006e55d4c3692c615cb279e7ae4
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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