Triisopropyl borate → Ethyl 1-((4-(5-(difluoro(phenyl)methyl)benzofuran-2-yl)-3-fluorophenyl)methyl)azetidine-3-carboxylate

HRID 2075197Notes

Reaction equation

HRID 2075197 reaction equation
[F:1][C:2]([F:18])([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:3]1[CH:4]=[CH:5][C:6]2[O:10][CH:9]=[CH:8][C:7]=2[CH:11]=1.C([Li])CCC.B(OC(C)C)(OC(C)C)OC(C)C.Br[C:38]1[CH:53]=[CH:52][C:41]([CH2:42][N:43]2[CH2:46][CH:45]([C:47]([O:49][CH2:50][CH3:51])=[O:48])[CH2:44]2)=[CH:40][C:39]=1[F:54].FC(F)(C1C=CC=CC=1)C1C=CC2OC(B(O)O)=CC=2C=1>C1COCC1>[F:18][C:2]([F:1])([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([C:38]3[CH:53]=[CH:52][C:41]([CH2:42][N:43]4[CH2:46][CH:45]([C:47]([O:49][CH2:50][CH3:51])=[O:48])[CH2:44]4)=[CH:40][C:39]=3[F:54])=[CH:8][C:7]=2[CH:11]=1

Participants

7

Reactant 5

HCID 21531Triisopropyl borateHCID 58415312Ethyl 1-(4-bromo-3-fluorobenzyl)azetidine-3-carboxylateHCID 584153605-(Difluoro(phenyl)methyl)benzofuranHCID 670921475-(Difluoro(phenyl)methyl)benzofuran-2-ylboronic acidHCID 178418339Butyllithium

Product 1

HCID 58415314Ethyl 1-((4-(5-(difluoro(phenyl)methyl)benzofuran-2-yl)-3-fluorophenyl)methyl)azetidine-3-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-(difluoro(phenyl)methyl)benzofuran (0.684 g, 2.8 mmol) in 28 mL THF at −78° C. under nitrogen was added butyllithium, 2.5M solution in hexanes (1.3 mL, 3.4 mmol) dropwise. The clear solution was allowed to stir for 30 min, at which point triisopropyl borate (0.97 mL, 4.2 mmol) was added. After 30 min, the bath was removed and the reaction allowed reaching ambient temperature. After 30 min, 28 mL 2N HCl was added, and the reaction was diluted with MTBE. The organic layer was washed with brine and dried with anhyd sodium sulfate, filtered, and concentrated to a ] clear oil. Hexanes was added to give a white solid, which was collected by filtration. A portion of the unpurified material was carried forward as follows: ethyl 1-(4-bromo-3-fluorobenzyl)azetidine-3-carboxylate (0.150 g, 0.474 mmol) and 5-(difluoro(phenyl)methyl)benzofuran-2-ylboronic acid (0.273 g, 0.949 mmol) were reacted according to Scheme B2 and general procedure F to give ethyl 1-((4-(5-(difluoro(phenyl)methyl)benzofuran-2-yl)-3-fluorophenyl)methyl)azetidine-3-carboxylate. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.94 (t, J=8.0 Hz, 1H), 7.89 (s, 1H), 7.76 (d, J=8.5 Hz, 1H), 7.45-7.60 (m, 6H), 7.38 (d, J=3.0 Hz, 1H), 7.26-7.33 (m, 2H), 4.10 (q, J=7.0 Hz, 2H), 3.63 (s, 2H), 3.43-3.51 (m, 2H), 3.20-3.38 (m, 3H), 1.19 (t, J=7.0 Hz, 3H).

Workup

  1. additionwas added
  2. customthe bath was removed
  3. customallowed reaching ambient temperature
  4. waitAfter 30 min
  5. addition28 mL 2N HCl was added
  6. additionthe reaction was diluted with MTBE
  7. washThe organic layer was washed with brine
  8. dry with materialdried with anhyd sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated to a ] clear oil
  11. additionHexanes was added
  12. customto give a white solid, which
  13. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-9f3adfeac2d141edacd5067f3d29d56a
Source dataset
uspto-grants-2011_04
Patent number
US07919519B2

Reaction notes

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