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

HRID 2276385Notes

Reaction equation

HRID 2276385 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:13][CH2:12][CH2:11][N:10]([C:14]([O-:16])=[O:15])[CH2:9]2)=[CH:4][CH:3]=1.[C:17]1([C:23]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[NH:24])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=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:25]1([C:23](=[N:24][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:5]([CH3:8])([CH3:6])[CH3:4])=[O:15])[CH2:9]3)=[CH:4][CH:3]=2)[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

5

Reactant 2

HCID 136809Benzophenone imineHCID 866615852-(4-Bromophenyl)morpholine-4-carboxylate

Product 1

HCID 86654632(S)-tert-butyl 2-(4-(diphenylmethyleneamino)phenyl)morpholine-4-carboxylateYield 148.3%

Reagents, catalysts & solvents 2

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
90 °C

Procedure

2-(4-bromophenyl)morpholine-4-carboxylate (47 g), diphenylmethanimine (29.9 g), BINAP (6.41 g) and Pd2(dba)3 (3.14 g) were dissolved under Argon in dry and de-aerated toluene (940 ml) and treated with sodium tert-butoxide (18.5 g). 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 room temperature 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 (silicagel, 20% ethylacetate/heptane). The combined and concentrated fractions were suspended in hexane, stirred for 17 h, filtered off and dried in vacuo to yield (S)-tert-butyl 2-(4-(diphenylmethyleneamino)phenyl)morpholine-4-carboxylate (54.1 g, 89%) as a yellow solid. MS (ISP): 443.3 ([M+H]+).

Workup

  1. customin dry
  2. additionde-aerated toluene (940 ml) and treated with sodium tert-butoxide (18.5 g)
  3. additionThe yellow/brown reaction mixture was diluted with toluene (700 ml)
  4. temperaturecooled to room temperature
  5. extractionextracted twice with water
  6. customThe organic layer was separated
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. additionThe crude product was diluted with 300 ml hexane
  10. stirringstirred for 1 h
  11. filtrationfiltered off
  12. customwas purified by column chromatography (silicagel, 20% ethylacetate/heptane)
  13. concentrationconcentrated fractions
  14. stirringstirred for 17 h
  15. filtrationfiltered off
  16. customdried in vacuo

Sources & evidence

ORD record
ord-b077857f4b854af2a0045b0b75207302
Source dataset
uspto-grants-2015_09
Patent number
US09132136B2

Reaction notes

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