Lithium Chloride → HCID 71240815, compound

HRID 1774607Notes

Reaction equation

HRID 1774607 reaction equation
C[Sn](C)(C)[Sn](C)(C)C.[Cl-].[Li+].Cl[C:12]1[CH:17]=[C:16]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH:25]([CH3:27])[CH3:26])=[C:20]([Cl:28])[CH:19]=2)[N:15]=[CH:14][N:13]=1.[CH3:29][O:30][C:31]([CH:33]1[CH2:37][C:36](OS(C(F)(F)F)(=O)=O)=[CH:35][N:34]1[C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])=[O:32]>C1COCC1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[CH3:29][O:30][C:31]([CH:33]1[CH2:37][C:36]([C:12]2[CH:17]=[C:16]([C:18]3[CH:23]=[CH:22][C:21]([O:24][CH:25]([CH3:27])[CH3:26])=[C:20]([Cl:28])[CH:19]=3)[N:15]=[CH:14][N:13]=2)=[CH:35][N:34]1[C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])=[O:32]

Participants

7

Reactant 4

HCID 433294Lithium ChlorideHCID 85161366HCID 85161366, compoundHCID 89396901HCID 89396901, compoundHCID 178477788HCID 178477788, compound

Product 1

HCID 71240815HCID 71240815, compoundYield 9%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

Hexamethyldistannane (5.6 ml, 2.7 mmol) and lithium chloride (0.34 g, 7.8 mmol) were added sequentially in one portion to a stirred solution of, 4-chloro-6-(3-chloro-4-isopropoxy-phenyl)-pyrimidine (0.75 g, 2.7 mmol) and 4-trifluoromethanesulfonyloxy-2,3-dihydro-pyrrole-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (1.0 g, 2.7 mmol) in THF (40 ml). The mixture was degassed with nitrogen for 5 minutes, after which time palladium tetrakis(triphenylphosphine) (0.31 g, 0.26 mmol) was added in one portion, the mixture was then heated to 70° C. and stirred at this temperature for 16 hours under a nitrogen atmosphere. After this time the reaction mixture was cooled to room temperature and partitioned between ethyl acetate (200 ml) and saturated potassium fluoride (50 ml). The organic layer was separated, washed sequentially with water (100 ml) then brine (100 ml) before being dried (MgSO4), filtered and concentrated. The resulting red gum was purified by flash column chromatography (elution: 80% EtOAc, 20% Heptane) to give the title compound (0.1 g, 9% yield) as a colourless oil. Tr=2.69 min m/z (ES+) (M+H+) 474.

Workup

  1. customThe mixture was degassed with nitrogen for 5 minutes
  2. temperatureAfter this time the reaction mixture was cooled to room temperature
  3. custompartitioned between ethyl acetate (200 ml) and saturated potassium fluoride (50 ml)
  4. customThe organic layer was separated
  5. washwashed sequentially with water (100 ml)
  6. dry with materialbrine (100 ml) before being dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resulting red gum was purified by flash column chromatography (elution: 80% EtOAc, 20% Heptane)

Sources & evidence

ORD record
ord-bda38543c00c42d784b7db45bbb755c1
Source dataset
uspto-grants-2016_02
Patent number
US09260422B2

Reaction notes

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