Cyclohexene, 1-((trimethylsilyl)oxy)- → Benzyl 3-hydroxy-3-(2-oxocyclohexyl)azetidine-1-carboxylate

HRID 605736

Reaction equation

HRID 605736 reaction equation
C[Si](C)(C)[O:3][C:4]1[CH2:9][CH2:8][CH2:7][CH2:6][CH:5]=1.[O:12]=[C:13]1[CH2:16][N:15]([C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])[CH2:14]1>O1CCCC1.[Ti](Cl)(Cl)(Cl)Cl>[OH:12][C:13]1([CH:5]2[CH2:6][CH2:7][CH2:8][CH2:9][C:4]2=[O:3])[CH2:14][N:15]([C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])[CH2:16]1

Participants

5

Reactant 2

HCID 81161Cyclohexene, 1-((trimethylsilyl)oxy)-HCID 10632047Benzyl 3-oxoazetidine-1-carboxylate

Product 1

HCID 67051703Benzyl 3-hydroxy-3-(2-oxocyclohexyl)azetidine-1-carboxylateYield 92.4%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 1-(trimethylsiloxy)cyclohexene (200 mg, 1.17 mmol) and benzyl 3-oxoazetidine-1-carboxylate (289 mg, 1.41 mmol), prepared using procedures similar to those described in Reference 3, in tetrahydrofuran (3.90 mL) was cooled to −78° C. for 10 minutes followed by the addition of titanium tetrachloride (0.13 mL, 1.17 mmol). The reaction mixture stirred for an additional 5 hours at −78° C. The mixture was quenched with aqueous sodium bicarbonate and the aqueous layer was extracted with ether (2×). The organic layer was separated, dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The residue was purified on silica gel chromatography column (3:2 hexanes/ethyl acetate) to afford benzyl 3-hydroxy-3-(2-oxocyclohexyl)azetidine-1-carboxylate (328 mg, 37%). 1H NMR (CDCl3): 7.28-7.34 (m, 5H), 5.08 (s, 2H), 4.02 (d, 1H), 3.89 (d, 1H), 3.87 (s, 1H), 3.55 (s, 1H), 2.71 (q, 1H), 2.29-2.43 (m, 2H), 2.11 (s, 2H), 1.95 (s, 1H), 1.66 (d, 3H); MS (EI) for C17H21NO4: 303 (MH+).

Workup

  1. customThe mixture was quenched with aqueous sodium bicarbonate
  2. extractionthe aqueous layer was extracted with ether (2×)
  3. customThe organic layer was separated
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated in vacuo
  7. customThe residue was purified on silica gel chromatography column (3:2 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-24b2100b35b04700a4d267dd31b14376
Source dataset
uspto-grants-2011_03
Patent number
US07915250B2

Linked notes

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