Dimethylformamide → HCID 67055293, compound

HRID 603013Notes

Reaction equation

HRID 603013 reaction equation
Br[C:2]1[CH:3]=[C:4]([C@H:9]([CH:14]2[CH2:17][N:16]([C@@H:18]([C:30]3[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=3)[C:19]3[CH:20]=[C:21]([CH:27]=[CH:28][CH:29]=3)[C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:15]2)[C:10]([F:13])([CH3:12])[CH3:11])[CH:5]=[C:6]([F:8])[CH:7]=1.[CH3:37][N:38](C=O)C>O.[C-]#N.[Zn+2].[C-]#N.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].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[Cl:36][C:33]1[CH:34]=[CH:35][C:30]([C@H:18]([N:16]2[CH2:17][CH:14]([C@@H:9]([C:4]3[CH:5]=[C:6]([F:8])[CH:7]=[C:2]([C:37]#[N:38])[CH:3]=3)[C:10]([F:13])([CH3:12])[CH3:11])[CH2:15]2)[C:19]2[CH:20]=[C:21]([CH:27]=[CH:28][CH:29]=2)[C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:31][CH:32]=1

Participants

7

Reactant 2

HCID 6228DimethylformamideHCID 67055385HCID 67055385, compound

Product 1

HCID 67055293HCID 67055293, compound

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of 5.64 g (9.77 mmol) of ethyl 3-[(S)-{3-[(1S)-1-(3-bromo-5-fluorophenyl)-2-fluoro-2-methylpropyl]azetidin-1-yl}(4-chlorophenyl)methyl]benzoate, 700 mg (5.96 mmol) of zinc cyanide, 179 mg (0.195 mmol) of tris(dibenzylideneacetone)dipalladium, and 270 mg (0.489 mmol) of DPPF in 99 mL of DMF and 1 mL of water was degassed with N2 for 1 h at rt. Then it was stirred at 125° C. After 12 h, the reaction mixture was concentrated to remove solvents. The residue was poured into 200 mL of CH2Cl2 and 50 mL of aq NaHCO3 (pH=7-8). The aqueous layer was extracted with CH2Cl2and the combined organic layer was dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography with hexanes/ethyl acetate to afford the title compound as a white solid; 1H-NMR(CDCl3) δ 1.23 (d, 3H, J1=21.7 Hz), 1.28 (d, 3H, J1=21.7 Hz), 1.40(t, 3H, J=7.1 Hz), 2.29(t, 1H, J=7.5 Hz), 2.85-2.95(m, 2H), 3.05(m, 1H), 3.18(m, 1H), 3.64 (t, 1H, J=6.7 Hz), 4.29(s, 1H), 4.37 (q, 2H, J1=14.2 Hz, J2=7.1 Hz), 7.16 (d, 1H, J=9.3 Hz), 7.23 (d, 1H, J=7.8 Hz), 7.27-7.38(m, 6H), 7.55 (d, 1H, J=7.8 Hz), 7.86 (d, 1H, J=7.7 Hz), 8.0 (s, 1H); Mass Spectrum: m/e=523, (M+1, 35Cl), 525 (M+1, 37Cl).

Workup

  1. customwas degassed with N2 for 1 h at rt
  2. concentrationthe reaction mixture was concentrated
  3. customto remove solvents
  4. additionThe residue was poured into 200 mL of CH2Cl2 and 50 mL of aq NaHCO3 (pH=7-8)
  5. extractionThe aqueous layer was extracted with CH2Cl2and the combined organic layer
  6. dry with materialwas dried over Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography with hexanes/ethyl acetate

Sources & evidence

ORD record
ord-792e15bb5c4b45fda4be069c6908e304
Source dataset
uspto-grants-2011_03
Patent number
US07906652B2

Reaction notes

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