Tetrahydrofuran → HCID 90310642, compound

HRID 1519148Notes

Reaction equation

HRID 1519148 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[O:9][CH3:10].[CH2:11]1[CH2:15][O:14][CH2:13][CH2:12]1.C([Mg]Cl)(C)C.C1(=O)CCC1>CCOCC>[F:8][C:4]1[C:3]([O:9][CH3:10])=[C:2]([C:15]2([OH:14])[CH2:11][CH2:12][CH2:13]2)[CH:7]=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 14496CyclobutanoneHCID 161026881-Bromo-3-fluoro-2-methoxybenzeneHCID 178418918HCID 178418918, compound

Product 1

HCID 90310642HCID 90310642, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

To a 3-L round-bottom flask were added a stire bar, 2-bromo-6-fluoroanisol (75.00 g, 370 mmol) and dry THF (1460 mL). The flask was purged with nitrogen and cooled to 0° Celsius before adding 2.0 M i-PrMgCl in THF (408 mL, 916 mmol) over the course of 15 min. The resultant mixture was stirred for 2 hours before adding cyclobutanone (34 mL, 455 mmol). The resultant mixture was stirred for 0.5 hour before diluting with Et2O (2.50 L) and washing with saturated NH4Cl followed by brine. The organic layer was isolated, dried over MgSO4, filtered and concentrated to dryness to give the crude product. Subjecting the residue to FCC gave the title compound (55.58 g). 1H NMR (400 MHz, CDCl3) δ 6.98-6.88 (m, 3H), 3.90-3.90 (s, 3H), 2.46-2.42 (m, 2H), 2.31-2.28 (m, 2H), 2.04 (m, 1H), 1.67-1.64 (m, 1H).

Workup

  1. additionTo a 3-L round-bottom flask were added a stire bar
  2. customThe flask was purged with nitrogen
  3. washwashing with saturated NH4Cl
  4. customThe organic layer was isolated
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customto give the crude product

Sources & evidence

ORD record
ord-c009f6532def42f8bb03a9fc10aa39fd
Source dataset
uspto-grants-2015_07
Patent number
US09073876B2

Reaction notes

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