Ammonium Chloride → HCID 67148208, compound

HRID 2428189Notes

Reaction equation

HRID 2428189 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:12][CH2:11][C@H:10]([O:13][C:14]3[C:19]([Cl:20])=[CH:18][C:17]([CH3:21])=[CH:16][C:15]=3[Cl:22])[CH2:9]2)=[N:6][CH:7]=1.[Li]CCCC.[CH3:28][O:29][C:30]([C:32]1[CH2:33][N:34]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH2:35][CH2:36][C:37]=1OS(C(F)(F)F)(=O)=O)=[O:31].[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>[CH3:28][O:29][C:30]([C:32]1[CH2:33][N:34]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH2:35][CH2:36][C:37]=1[C:2]1[CH:7]=[N:6][C:5]([N:8]2[CH2:12][CH2:11][C@H:10]([O:13][C:14]3[C:19]([Cl:20])=[CH:18][C:17]([CH3:21])=[CH:16][C:15]=3[Cl:22])[CH2:9]2)=[CH:4][CH:3]=1)=[O:31]

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 152219361-Tert-butyl 3-methyl 4-(trifluoromethanesulfonyloxy)-1,2,5,6-tetrahydropyridine-1,3-dicarboxylateHCID 67148219HCID 67148219, compoundHCID 178418339Butyllithium

Product 1

HCID 67148208HCID 67148208, compoundYield 57.3%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A sol. of (S)-5-bromo-2-[3-(2,6-dichloro-4-methyl-phenoxy)-pyrrolidin-1-yl]-pyridine (8.52 g, 21.2 mmol) in THF (212 mL) at −78° C. was treated with BuLi (1.6M in hexane, 22.1 mL, 35.3 mmol). The mixture was stirred −78° C. for 30 min, and ZnCl2 (1.03M in THF, 41.1 mL, 42.4 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; 9.17 g, 23.5 mmol) in THF (5 mL), and Pd(PPh3)4 (816 mg, 0.701 mmol) were added. The mixture was rapidly heated to 75° C., and stirred at this temperature for 1 h. The mixture was allowed to cool to rt, and aq. sat. NH4Cl was added. The mixture was extracted with EtOAc. The org. extracts were washed with aq. sat. NH4Cl, dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the crude by FC (heptane→heptane:EtOAc 65:35) yielded the title compound (6.83 g, 52%). LC-MS: tR=0.92 min, ES+: 562.36.

Workup

  1. temperatureto warm up to rt
  2. temperatureThe mixture was rapidly heated to 75° C.
  3. stirringstirred at this temperature for 1 h
  4. temperatureto cool to rt
  5. extractionThe mixture was extracted with EtOAc
  6. washextracts were washed with aq. sat. NH4Cl
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customthe solvents were removed under reduced pressure
  10. customPurification of the crude by FC (heptane→heptane:EtOAc 65:35)

Sources & evidence

ORD record
ord-1c3a25d845d74cada492ad511f4ffac6
Source dataset
uspto-grants-2011_06
Patent number
US07968720B2

Reaction notes

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