Ammonium Chloride → HCID 67148313, compound

HRID 2428170Notes

Reaction equation

HRID 2428170 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12](Br)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li]CCCC.[CH3:21][O:22][C:23]([C:25]1[CH2:26][N:27]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:28][CH2:29][C:30]=1OS(C(F)(F)F)(=O)=O)=[O:24].[NH4+].[Cl-]>C1COCC1.[Cl-].[Cl-].[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:21][O:22][C:23]([C:25]1[CH2:26][N:27]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:28][CH2:29][C:30]=1[C:12]1[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:10][CH:11]=1)=[O:24]

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 1388351-Bromo-4-phenylmethoxybenzeneHCID 152219361-Tert-butyl 3-methyl 4-(trifluoromethanesulfonyloxy)-1,2,5,6-tetrahydropyridine-1,3-dicarboxylateHCID 178418339Butyllithium

Product 1

HCID 67148313HCID 67148313, compoundYield 98.2%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a sol. of 4-benzoxy-bromo-benzene (18.4 g, 70.0 mmol) in THF (450 mL) at −78° C. was added BuLi (1.6M in hexane, 50.0 mL, 80.0 mmol). The mixture was stirred for 30 min at −78° C., and ZnCl2 (1M in THF, 86 mL, 86 mmol) was added. The mixture was allowed to warm up to rt. A sol. of 4-trifluoromethanesulfonyloxy-5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (WO 2004/002957; 19.5 g, 50.0 mmol) in THF (20 mL) and Pd(PPh3)4 (1.43 g, 1.23 mmol) were added. The mixture was quickly heated to 50° C., and stirred at this temperature for 40 min. Aq. sat. NH4Cl was added, and the mixture was extracted with EtOAc (3×). The combined org. extracts were washed with brine, dried over Na2SO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (EtOAc/heptane 1:9→2:8) yielded the title compound (20.8 g, 98%). LC-MS: tR=1.12 min; ES+: 424.25.

Workup

  1. temperatureto warm up to rt
  2. temperatureThe mixture was quickly heated to 50° C.
  3. stirringstirred at this temperature for 40 min
  4. extractionthe mixture was extracted with EtOAc (3×)
  5. washextracts were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customthe solvents were removed under reduced pressure
  9. customPurification of the residue by FC (EtOAc/heptane 1:9→2:8)

Sources & evidence

ORD record
ord-4391cf6dcfc2428fb28e3ad2ee57ca16
Source dataset
uspto-grants-2011_06
Patent number
US07968720B2

Reaction notes

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