2,6-Lutidine → (S)-benzyl 3-(4-(benzyloxy)phenyl)-2-(1,3-dioxoisoindolin-2-yloxy)propanoate

HRID 576880Notes

Reaction equation

HRID 576880 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C@@H:16]([OH:27])[C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.N1C(C)=CC=CC=1C.O[N:52]1[C:56](=[O:57])[C:55]2=[CH:58][CH:59]=[CH:60][CH:61]=[C:54]2[C:53]1=[O:62].C(N(CC)CC)C>ClCCl>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C@H:16]([O:27][N:52]2[C:56](=[O:57])[C:55]3[C:54](=[CH:61][CH:60]=[CH:59][CH:58]=3)[C:53]2=[O:62])[C:17]([O:19][CH2:20][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)=[O:18])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 79372,6-LutidineHCID 8471TriethylamineHCID 10665N-HydroxyphthalimideHCID 67749Trifluoromethanesulfonic anhydrideHCID 86663945HCID 86663945, compound

Product 1

HCID 86663946(S)-benzyl 3-(4-(benzyloxy)phenyl)-2-(1,3-dioxoisoindolin-2-yloxy)propanoateYield 59.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-benzyl 3-(4-(benzyloxy)phenyl)-2-hydroxypropanoate (Compound XLIII-1) 18.1 g (50.0 mmol) in dichloromethane 80 ml, trifluoromethanesulfonic anhydride 10.1 ml (60.0 mmol) and 2,6-lutidine 8.74 ml (75.0 mmol) were added and the mixture was stirred at room temperature for 0.5 hr. N-hydroxyphthalimide 8.16 g (50.0 mmol) and triethylamine 10.5 ml (75.0 mmol) were added to the reaction mixture and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo and diluted with ethyl acetate 500 ml and washed with saturated sodium bicarbonate solution 500 ml, water 500 ml and brine 500 ml. The organic phase was dried over magnesium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified on silica gel column chromatography (Merck 60N spherical, neutral elution by n-hexane:ethyl acetate=90:10 to 70:30) to obtain the title compound 15.0 g (yield 59%).

Workup

  1. stirringthe mixture was stirred at room temperature overnight
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. additiondiluted with ethyl acetate 500 ml
  4. washwashed with saturated sodium bicarbonate solution 500 ml, water 500 ml and brine 500 ml
  5. dry with materialThe organic phase was dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customthe residue was purified on silica gel column chromatography (Merck 60N spherical, neutral elution by n-hexane:ethyl acetate=90:10 to 70:30)

Sources & evidence

ORD record
ord-6971f138715e4e55a7e539739f99ce8e
Source dataset
uspto-grants-2015_05
Patent number
US09040531B2

Reaction notes

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