Benzophenone imine → (R)-tert-butyl 2-(4-(diphenylmethyleneamino)-2-fluorophenyl)morpholine-4-carboxylate

HRID 2403332Notes

Reaction equation

HRID 2403332 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)=[C:4]([F:21])[CH:3]=1.[C:22](=[NH:35])([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1>[C:23]1([C:22](=[N:35][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)=[C:4]([F:21])[CH:3]=2)[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

5

Reactant 3

HCID 136809Benzophenone imineHCID 23676156Sodium t-butoxideHCID 68325672(+)-(R)-tert-butyl 2-(4-bromo-2-fluorophenyl)morpholine-4-carboxylate

Product 1

HCID 86671413(R)-tert-butyl 2-(4-(diphenylmethyleneamino)-2-fluorophenyl)morpholine-4-carboxylate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred solution of (+)-(R)-tert-butyl 2-(4-bromo-2-fluorophenyl)morpholine-4-carboxylate (4.3 g) and benzophenone imine (2.2 ml) in toluene (20 ml) was added sodium tert-butoxide (1.84 g). The reaction mixture was purged with argon for 10 min. (R)-(+)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (743 mg) and tris(dibenzylideneacetone)dipalladium(0) (328 mg) were added and the reaction mixture was heated to 90° C. and stirred for 90 min. The reaction mixture was poured into water and extracted twice with EtOAc. The organic layers were dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel; gradient: 0% to 40% EtOAc in hexanes) to afford (R)-tert-butyl 2-(4-(diphenylmethyleneamino)-2-fluorophenyl)morpholine-4-carboxylate 5.95 g, quant.) as a yellow amorphous solid. MS (ISP): 461.2 ([M+H]+).

Workup

  1. customThe reaction mixture was purged with argon for 10 min. (R)-(+)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (743 mg) and tris(dibenzylideneacetone)dipalladium(0) (328 mg)
  2. additionwere added
  3. additionThe reaction mixture was poured into water
  4. extractionextracted twice with EtOAc
  5. dry with materialThe organic layers were dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography (silica gel; gradient: 0% to 40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-5826e4f85de64589933075e48cb292b7
Source dataset
uspto-grants-2014_08
Patent number
US08802673B2

Reaction notes

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