Phthalimide → (2S,3R)-Benzyl 2-((1,3-dioxoisoindolin-2-yl)methyl)-3-methylpiperidine-1-carboxylate

HRID 60884Notes

Reaction equation

HRID 60884 reaction equation
C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.O[CH2:35][C@@H:36]1[C@H:41]([CH3:42])[CH2:40][CH2:39][CH2:38][N:37]1[C:43]([O:45][CH2:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)=[O:44].[C:53]1(=[O:63])[NH:57][C:56](=[O:58])[C:55]2=[CH:59][CH:60]=[CH:61][CH:62]=[C:54]12>C1COCC1>[O:58]=[C:56]1[C:55]2[C:54](=[CH:62][CH:61]=[CH:60][CH:59]=2)[C:53](=[O:63])[N:57]1[CH2:35][C@@H:36]1[C@H:41]([CH3:42])[CH2:40][CH2:39][CH2:38][N:37]1[C:43]([O:45][CH2:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)=[O:44]

Participants

6

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 117731459(2S,3R)-benzyl 2-(hydroxymethyl)-3-methylpiperidine-1-carboxylate

Product 1

HCID 117731460(2S,3R)-Benzyl 2-((1,3-dioxoisoindolin-2-yl)methyl)-3-methylpiperidine-1-carboxylateYield 110%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of PPh3 (21.5 g, 82 mmol) in 30 ml of THF was cooled to 0° C. DIAD (16.1 mL, 82 mmol) was then added dropwise and reaction stirred for 20 min. A solution of (2S,3R)-benzyl 2-(hydroxymethyl)-3-methylpiperidine-1-carboxylate (8.7 g, 32.9 mmol) in 15 mL THF was then added dropwise and stirred at 0° C. for 30 min. Phthalimide (6.3 g, 42.7 mmol) was then added and the reaction was warmed to rt overnight. The resulting suspension was concentrated in vacuo, diluted with EtOAc, washed with water and brine, dried (MgSO4), and concentrated. The crude residue was purified by chromatography on silica gel (EtOAc/hexanes) to give the title compound (14.2 g, 110%, DIAD contamination), which was used without further purification. 1H NMR (CDCl3, 400 MHz) δ 7.72-7.71 (m, 1H), 7.62-7.60 (m, 3H), 7.17-7.13 (m, 3H), 7.05-7.04 (m, 1H), 6.98-6.96 (m, 1H), 4.76-4.69 (m, 1H), 4.54-4.39 (m, 1H), 4.03-3.98 (m, 2H), 3.63-3.54 (m, 1H), 3.25-3.07 (m, 1H), 1.91-1.80 (m, 1H), 1.73-1.54 (m, 2H), 1.47-1.25 (m, 2H), 1.07-1.04 (m, 3H). ESI-MS (m/z): 263.93 [M+1]+.

Workup

  1. customreaction
  2. stirringstirred at 0° C. for 30 min
  3. concentrationThe resulting suspension was concentrated in vacuo
  4. additiondiluted with EtOAc
  5. washwashed with water and brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customThe crude residue was purified by chromatography on silica gel (EtOAc/hexanes)

Sources & evidence

ORD record
ord-32fcdd76943d40d3910775682807c05f
Source dataset
uspto-grants-2016_09
Patent number
US09440982B2

Reaction notes

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