Trimethyl phosphite → HCID 22396793, compound

HRID 1370476Notes

Reaction equation

HRID 1370476 reaction equation
[C:1]([N:9]1[CH2:22][CH2:21][C:20]2[C:19]3[C:18](B4OC(C)(C)C(C)(C)O4)=[CH:17][CH:16]=[CH:15][C:14]=3[NH:13][C:12]=2[CH2:11][CH2:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=1[C:47]([F:50])([F:49])[F:48].COP(OC)OC>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:1]([N:9]1[CH2:22][CH2:21][C:20]2[C:19]3[C:18]([C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=4[C:47]([F:50])([F:49])[F:48])=[CH:17][CH:16]=[CH:15][C:14]=3[NH:13][C:12]=2[CH2:11][CH2:10]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 8472Trimethyl phosphiteHCID 9806Benzene, 1-bromo-2-(trifluoromethyl)-HCID 62657Potassium Phosphate, TribasicHCID 22396616HCID 22396616, compound

Product 1

HCID 22396793HCID 22396793, compoundYield 95.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

3-Benzoyl-10-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (2.50 g, 6.00 mmol), triturated potassium phosphate (3.01 g, 14.2 mmol) and tris(dibenzylideneacetone)dipalladium(0) (0.562 g, 0.613 mmol) were combined in dioxane (63 mL) at rt under N2. 2-Bromobenzotrifluoride (0.98 mL, 1.62 g, 7.21 mmol) and trimethylphosphite (0.22 mL, 0.231 g, 1.86 mmol) were added to the reaction mixture by syringe. Ar was bubbled through the reaction mixture for 20 min. The reaction mixture was heated to reflux for 22 h. The reaction mixture was concentrated and the residue was taken up in toluene (150 mL) and H2O (200 mL). The layers were separated and the aqueous layer was extracted with toluene (1×100 mL, 1×50 mL). The combined organic layers were dried over MgSO4, filtered and concentrated. The crude product (3.90 g) was chromatographed (SiO2 250 g, eluted with 2:1 toluene:EtOAc) to yield 3-benzoyl-10-[2-(trifluoromethyl)phenyl]-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (2.48 g) in 95% yield. IR (diffuse reflectance) 3294, 1617, 1575, 1461, 1439, 1423, 1346, 1334, 1316, 1276, 1266, 1259, 1178, 1170, 1126, 1113, 1105, 1058, 1034, 792, 775, 755, 719, 701, 626 cm−1; MS (ESI+) for C26H21F3N2O m/z 435.0 (M+H)+; Anal. Calcd for C26H21F3N2O: C, 71.88; H, 4.87; N, 6.45; found: C, 71.94; H, 4.93; N, 6.48.

Workup

  1. customAr was bubbled through the reaction mixture for 20 min
  2. temperatureThe reaction mixture was heated
  3. temperatureto reflux for 22 h
  4. concentrationThe reaction mixture was concentrated
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with toluene (1×100 mL, 1×50 mL)
  7. dry with materialThe combined organic layers were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product (3.90 g) was chromatographed
  11. wash(SiO2 250 g, eluted with 2:1 toluene:EtOAc)

Sources & evidence

ORD record
ord-de8887d047b248e58489b885e6ff81f7
Source dataset
uspto-grants-2003_06
Patent number
US06583135B2

Reaction notes

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