3-Oxetanone → HCID 86703625, compound

HRID 1849744Notes

Reaction equation

HRID 1849744 reaction equation
[C:1]12([CH2:11][O:12][C:13]3[C:25](I)=[CH:24][C:16]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[C:15]([F:27])[CH:14]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[Cl-].[Li+].C([Mg]Cl)(C)C.[O:35]1[CH2:38][C:37](=[O:39])[CH2:36]1>O1CCCC1>[C:1]12([CH2:11][O:12][C:13]3[C:25]([C:37]4([OH:39])[CH2:38][O:35][CH2:36]4)=[CH:24][C:16]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[C:15]([F:27])[CH:14]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2

Participants

5

Reactant 3

HCID 150242543-OxetanoneHCID 86703626HCID 86703626, compoundHCID 178461733HCID 178461733, compound

Product 1

HCID 86703625HCID 86703625, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-40 °C

Procedure

To a solution of tert-butyl 4-(adamantan-1-ylmethoxy)-2-fluoro-5-iodobenzoate (0.973 g, 2.00 mmol) in anhydrous tetrahydrofuran (10 mL) was added isopropylmagnesium chloride lithium chloride complex (1.30 M solution in tetrahydrofuran, 1.76 mL, 2.20 mmol) at −40° C. The reaction mixture was stirred for 1 hour at −40° C., after which oxetan-3-one (0.432 g, 6.00 mmol) was added. The reaction mixture was allowed to warm to ambient temperature and stirred for 1 hour. After quenched with saturated ammonium chloride solution (10 mL), the mixture was extracted with ethyl acetate (2×20 mL). The combined organic phase was washed with brine (5 mL); dried over sodium sulfate, and filtered. Concentration of the filtrate in vacuo gave a residue which was purified by silica gel column chromatography using 0-50% ethyl acetate in hexanes as eluent to afford the title compound as an amorphous solid (0.336 g, 39%): 1H NMR (300 MHz, CDCl3) δ 7.75 (d, J=8.2 Hz, 1H), 6.60 (d, J=12.3 Hz, 1H), 5.01 (d, J=6.9 Hz, 2H), 4.84 (d, J=7.0 Hz, 2H), 3.86 (s, 1H), 3.52 (s, 2H), 2.05-1.94 (m, 3H), 1.78-1.55 (m, 12H), 1.54 (s, 9H).

Workup

  1. temperatureto warm to ambient temperature
  2. stirringstirred for 1 hour
  3. customAfter quenched with saturated ammonium chloride solution (10 mL)
  4. extractionthe mixture was extracted with ethyl acetate (2×20 mL)
  5. washThe combined organic phase was washed with brine (5 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customConcentration of the filtrate in vacuo gave a residue which
  9. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-5544a680010d45c29fb5f6cf05881bca
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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