3-Oxo-azetidine-1-carboxylic acid tert-butyl ester → HCID 67051632, compound

HRID 1809002Notes

Reaction equation

HRID 1809002 reaction equation
[CH3:1][C:2]1[N:3]([CH2:7][O:8][CH2:9][CH2:10][Si:11]([CH3:14])([CH3:13])[CH3:12])[CH:4]=[CH:5][N:6]=1.C([Li])CCC.[O:20]=[C:21]1[CH2:24][N:23](C(OC(C)(C)C)=O)[CH2:22]1>O1CCCC1>[CH3:14][Si:11]([CH3:13])([CH3:12])[CH2:10][CH2:9][O:8][CH2:7][N:3]1[CH:4]=[CH:5][N:6]=[C:2]1[CH2:1][C:21]1([OH:20])[CH2:24][NH:23][CH2:22]1

Participants

5

Reactant 3

HCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterHCID 17920097107750-76-5HCID 178418339Butyllithium

Product 1

HCID 67051632HCID 67051632, compoundYield 56.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 2-methyl-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole (0.5 g, 2.3 mmol) (prepared using procedures similar to those described in Clader et. al. J. of Med. Chem. 1995, 38(10), 1600-7) in tetrahydrofuran (5 mL) was cooled to −78° C., and n-butyllithium was added (2.5 M in hexanes, 0.990 mL, 2.5 mmol). After 2 hours, 1,1-dimethylethyl 3-oxoazetidine-1-carboxylate (0.60 g, 3.5 mmol), prepared using procedures similar to those described in Example 3, in 2.0 mL tetrahydrofuran was added and the solution was allowed to warm to room temperature and stirred overnight. The reaction mixture was quenched with an excess of saturated aqueous ammonium chloride solution and partitioned between water and ethyl acetate. The layers were separated and the aqueous layer was extracted with ethyl acetate (2×10 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. Column chromatography (silica gel, 3:1 hexanes/ethyl acetate) gave 0.37 g (41%) of 3-{[1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazol-2-yl]methyl}azetidin-3-ol: 1H NMR (400 MHz, CDCl3): 6.96-6.92 (m, 1H), 5.23 (s, 2H), 3.98 (d, 2H), 3.79 (d, 2H), 3.52-3.47 (m, 2H), 3.13 (s, 2H), 1.43 (s, 9H), 0.94-0.88 (m, 2H), 0.00 (s, 9H).

Workup

  1. additionwas added
  2. customThe reaction mixture was quenched with an excess of saturated aqueous ammonium chloride solution
  3. custompartitioned between water and ethyl acetate
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with ethyl acetate (2×10 mL)
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a2d5fa3eba8249d8bd4b1f56cf08364a
Source dataset
uspto-grants-2013_01
Patent number
US08362002B2

Reaction notes

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