Ammonium Chloride → HCID 118022207, compound

HRID 1498874Notes

Reaction equation

HRID 1498874 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[Li]CCCC.[CH3:26][C:27]([S@:30](/[N:32]=[C:33](/[C:38]1[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=1)\[C:34]([F:37])([F:36])[F:35])=[O:31])([CH3:29])[CH3:28].[NH4+].[Cl-]>C1COCC1>[C:27]([S@:30]([NH:32][C@:33]([C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[N:6][CH:7]=1)([C:38]1[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=1)[C:34]([F:35])([F:36])[F:37])=[O:31])([CH3:29])([CH3:26])[CH3:28]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 21914476tert-Butyl 4-(5-bromopyrimidin-2-yl)piperazine-1-carboxylateHCID 118023402HCID 118023402, compoundHCID 178418339Butyllithium

Product 1

HCID 118022207HCID 118022207, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

tert-Butyl 4-(5-bromopyrimidin-2-yl)piperazine-1-carboxylate (0.242 g, 0.705 mmol) was taken up in THF (3.5 mL) and cooled to −78° C. A solution of nBuLi, 2.5 M in hexanes (0.31 mL, 0.775 mmol) was added at a fast dropwise rate from a syringe. The resulting mixture was stirred at −78° C. for 15 minutes. A solution of (R,Z)-2-methyl-N-(2,2,2-trifluoro-1-(4-fluorophenyl)ethylidene)propane-2-sulfinamide (0.225 g, 0.762 mmol) in THF (0.5 mL) was added at a fast dropwise rate from a syringe. The reaction mixture was stirred at −78° C. for 5 minutes before warming to room temperature. After 45 minutes, saturated NH4Cl was added and the products extracted into EtOAc (×2). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. Purification of the residue by MPLC (0-80% EtOAc-hexanes) gave tert-butyl 4-(5-((S)-1-(((R)-tert-butylsulfinyl)amino)-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl)pyrimidin-2-yl)piperazine-1-carboxylate (304 mg, 0.543 mmol, 77% yield) as a pale yellow gum. The absolute stereochemistry was assigned randomly.

Workup

  1. stirringThe reaction mixture was stirred at −78° C. for 5 minutes
  2. temperaturebefore warming to room temperature
  3. waitAfter 45 minutes
  4. extractionthe products extracted into EtOAc (×2)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification of the residue by MPLC (0-80% EtOAc-hexanes)

Sources & evidence

ORD record
ord-8d17ed5b66204cd3b527b802a3cde11e
Source dataset
uspto-grants-2015_12
Patent number
US09200002B2

Reaction notes

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