Benzophenone imine → (S)-tert-butyl 2-(4-(diphenylmethyleneamino)phenyl)morpholine-4-carboxylate

HRID 1520762Notes

Reaction equation

HRID 1520762 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[O:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]2)=[CH:4][CH:3]=1.[C:21]1([C:27]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[NH:28])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[C:21]1([C:27](=[N:28][C:2]2[CH:7]=[CH:6][C:5]([C@@H:8]3[O:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]3)=[CH:4][CH:3]=2)[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

7

Reactant 3

HCID 136809Benzophenone imineHCID 23676156Sodium t-butoxideHCID 58097875tert-butyl (2S)-2-(4-bromophenyl)morpholine-4-carboxylate

Product 1

HCID 86654632(S)-tert-butyl 2-(4-(diphenylmethyleneamino)phenyl)morpholine-4-carboxylateYield 89.2%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
90 °C

Procedure

(S)-tert-butyl 2-(4-bromophenyl)morpholine-4-carboxylate (47 g, 137 mmol), diphenylmethanimine (29.9 g, 27.6 m, 165 mmol), BINAP (6.41 g, 10.3 mmol) and Pd2(dba)3 (3.14 g, 3.43 mmol) were dissolved under Argon in dry and de-aerated toluene (940 ml) and treated with sodium tert-butoxide (18.5 g, 192 mmol). The dark brown mixture was stirred at 90° C. for 18 h. The yellow/brown reaction mixture was diluted with toluene (700 ml), cooled to rt and extracted twice with water. The organic layer was separated, dried over magnesium sulfate and concentrated in vacuo. The crude product was diluted with 300 ml hexane, stirred for 1 h and filtered off, leading to an orange solid (68 g) which was purified by column chromatography (1.3 Kg silicagel, 20% ethylacetate/heptane). The combined and concentrated fractions were suspended in hexane, stirred for 17 h, filtered off andf dried in high vacuo, to yield 54.1 g (89%) yellow solid. MS (ISP): 443.3 ([M+H]+).

Workup

  1. customin dry
  2. temperaturecooled to rt
  3. extractionextracted twice with water
  4. customThe organic layer was separated
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. additionThe crude product was diluted with 300 ml hexane
  8. stirringstirred for 1 h
  9. filtrationfiltered off
  10. customwas purified by column chromatography (1.3 Kg silicagel, 20% ethylacetate/heptane)
  11. concentrationconcentrated fractions
  12. stirringstirred for 17 h
  13. filtrationfiltered off
  14. customandf dried in high vacuo

Sources & evidence

ORD record
ord-0393a1b975af43fdb366137984c551b9
Source dataset
uspto-grants-2015_07
Patent number
US09073911B2

Reaction notes

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