Lithium Chloride → HCID 89996154, compound

HRID 2276039Notes

Reaction equation

HRID 2276039 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH2:9][OH:10])[C:5](I)=[N:6][CH:7]=1.C([Mg]Cl)(C)C.[Li+].[Cl-].[C:18]([N:25]1[CH2:28][C:27](=[O:29])[CH2:26]1)([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19]>C1COCC1>[C:21]([O:20][C:18]([N:25]1[CH2:28][C:27]([C:5]2[C:4]([CH2:9][OH:10])=[CH:3][C:2]([Br:1])=[CH:7][N:6]=2)([OH:29])[CH2:26]1)=[O:19])([CH3:24])([CH3:22])[CH3:23]

Participants

6

Reactant 4

HCID 433294Lithium ChlorideHCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterHCID 89996153HCID 89996153, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 89996154HCID 89996154, compoundYield 45.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of (5-bromo-2-iodo-pyridin-3-yl)-methanol (9.5 g, 30.2 mmol, 1 eq) in dry THF (100 mL) was added i-PrMgCl.LiCl complex (1.3M in THF, 55.9 mL, 72.6 mmol, 2.4 eq) at −20° C. in drop wise manner over period of 20 minutes. Predissolved solution of N-boc-3-azetidinone (6.22 g, 36.3 mmol, 1.2 eq) in dry THF (80 mL) was added at −20° C. to above reaction mixture. Resulting reaction mixture was stirred at room temperature for 16 hours under nitrogen atmosphere. After maximum consumption of starting material, reaction mixture was cooled to 0° C. and quenched with 10% citric acid solution (20 mL), diluted with water (150 mL) and extracted with ethyl acetate (3×100 mL). Combined organic phase was washed with brine solution (100 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure to get yellowish sticky mass (18.2 g, crude). Crude compound was purified by column chromatography by using silica gel (100-200 mesh). Desired compound was eluted by 35% ethyl acetate in hexane to afford title compound as pale yellow thick oil (4.9 g, 45%). 1H NMR (400 MHz, CDCl3) δ: 1.43 (s, 9H), 3.12 (s, 1H), 4.13 (d, J=9.92 Hz, 2H), 4.54 (bs, 2H), 4.71-4.73 (m, 3H), 7.93 (d, J=2.12 Hz, 1H), 8.53 (d, J=3.00 Hz, 1H). LC-MS (m/z): 358.9 (M+H).

Workup

  1. customResulting
  2. customreaction mixture
  3. customAfter maximum consumption of starting material, reaction mixture
  4. temperaturewas cooled to 0° C.
  5. customquenched with 10% citric acid solution (20 mL)
  6. additiondiluted with water (150 mL)
  7. extractionextracted with ethyl acetate (3×100 mL)
  8. washCombined organic phase was washed with brine solution (100 mL)
  9. dry with materialdried over anhydrous Na2SO4
  10. concentrationconcentrated under reduced pressure
  11. customto get yellowish sticky mass (18.2 g, crude)
  12. customCrude compound was purified by column chromatography
  13. washDesired compound was eluted by 35% ethyl acetate in hexane

Sources & evidence

ORD record
ord-eba0d1b1da1d4e0b8e52a1027ed534a0
Source dataset
uspto-grants-2015_09
Patent number
US09131697B2

Reaction notes

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