Ammonium Chloride → HCID 58431035, compound

HRID 1040516Notes

Reaction equation

HRID 1040516 reaction equation
[C:1]([C@@H:5]1[N:9]([C:10]2[CH:15]=[C:14]([Cl:16])[C:13]([F:17])=[C:12]([Cl:18])[CH:11]=2)[C:8](=[O:19])[C@@H:7]([CH3:20])[N:6]1[C:21](=[O:26])[C:22]([F:25])([F:24])[F:23])([CH3:4])([CH3:3])[CH3:2].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[C:37]([C:39]1[CH:46]=[CH:45][C:42]([CH2:43]Br)=[CH:41][CH:40]=1)#[N:38].[NH4+].[Cl-]>C1COCC1.CCOC(C)=O.O>[C:1]([C@H:5]1[N:6]([C:21](=[O:26])[C:22]([F:24])([F:23])[F:25])[C@@:7]([CH2:43][C:42]2[CH:45]=[CH:46][C:39]([C:37]#[N:38])=[CH:40][CH:41]=2)([CH3:20])[C:8](=[O:19])[N:9]1[C:10]1[CH:15]=[C:14]([Cl:16])[C:13]([F:17])=[C:12]([Cl:18])[CH:11]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 869964-(Bromomethyl)benzonitrileHCID 2733832Lithium HexamethyldisilazideHCID 58430945HCID 58430945, compound

Product 1

HCID 58431035HCID 58431035, compoundYield 105.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-5 °C

Procedure

To a solution of (2S,5R)-2-tert-butyl-3-(3,5-dichloro-4-fluoro-phenyl)-5-methyl-1-(2,2,2-trifluoro-acetyl)-imidazolidin-4-one (158.4 g, 0.382 mol) in anhydrous THF (382 mL) under a nitrogen atmosphere at −20° C. was added a solution of LiHMDS (1.0 M in THF, 401 mL, 0.401 mol) over 50 min. The internal temperature increased to −5° C. over the course of this addition. Stirring was continued at this temperature for an additional hour. The reaction was cooled to −10° C. and a solution of 4-cyanobenzyl bromide (78.5 g, 401 mmol) in anhydrous THF (400 mL) was added over 50 min. The reaction temperature had increased to 0° C. over the course of the addition. Stirring was continued for 2 h while the reaction was allowed to warm to 10° C. To the reaction mixture was added saturated aqueous NH4Cl (200 mL), water (800 mL), and EtOAc (1 L). The layers were separated and the aqueous layer was extracted with EtOAc (1 L). The combined organic layers were dried with MgSO4 and concentrated in vacuo to give 214.2 g of the title compound as a tan/brown solid, m/z 571.3 [M+MeCN+H]+.

Workup

  1. waitwas continued at this temperature for an additional hour
  2. temperatureThe reaction was cooled to −10° C.
  3. temperatureThe reaction temperature had increased to 0° C. over the course of the addition
  4. stirringStirring
  5. temperatureto warm to 10° C
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted with EtOAc (1 L)
  8. dry with materialThe combined organic layers were dried with MgSO4
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-29d4d02409ac40ac9f4645788388f018
Source dataset
uspto-grants-2013_10
Patent number
US08552205B2

Reaction notes

Loading…