Formaldehyde → HCID 57475770, compound

HRID 2060763Notes

Reaction equation

HRID 2060763 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:8]2[CH2:9][CH2:10][O:11][CH2:12][CH:13]=2)[CH:5]=[CH:6][CH:7]=1.[CH2:14]=[O:15].[Cl-].C[Al+]C>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]([CH2:14][OH:15])[CH2:12][O:11][CH2:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 712Formaldehyde2×HCID 16686359Dimethylalumanylium chloride2×HCID 57475766HCID 57475766, compound

Product 1

HCID 57475770HCID 57475770, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A 0° C. solution of 4-(3-bromophenyl)-3,6-dihydro-2H-pyran (0.50 g, 2.09 mmol) in CH2Cl2 (15 mL) is treated with paraformaldehyde (0.208 g, 2.20 mmol) and stirred for 5 minutes at 0° C. A 1 M solution of dimethylaluminum chloride in hexanes (3.03 mL, 3.03 mmol) is added drop-wise to the slurry. The reaction is warmed to room temperature and stirred for 1 hour. The reaction is cooled to 0° C. and more paraformaldehyde (0.208 g, 2.20 mmol) and 1 M solution of dimethylaluminum chloride in hexanes (3.03 mL, 3.03 mmol) is added. The reaction is warmed to room temperature and stirred overnight. The reaction is quenched by pouring into an ice/1 N HCl mixture and is extracted three times with EtOAc. The combined organic layers are dried over Na2SO4 and the solvent is removed under reduced pressure to afford a residue that is purified on silica gel chromatography eluting with a linear gradient of 5% to 100% EtOAc in hexanes to give the title compound (0.315 g, 53%). 1H NMR (400 MHz, CDCl3) δ 7.50 (t, J=2.0 Hz, 1H), 7.40 (dd, J=2.2, 7.9 Hz, 1H), 7.29-7.27 (m, 1H), 7.20 (t, J=7.9 Hz, 1H), 6.11 (t, J=2.9 Hz, 1H), 4.32-4.29 (m, 2H), 4.28-4.25 (m, 1H), 3.76 (dd, J=3.1, 11.4 Hz, 1H), 3.70-3.64 (m, 2H), 2.70 (d, J=2.2 Hz, 1H), 1.89 (dd, J=4.6, 6.4 Hz, 1H).

Workup

  1. temperatureThe reaction is warmed to room temperature
  2. stirringstirred for 1 hour
  3. temperatureThe reaction is cooled to 0° C.
  4. temperatureThe reaction is warmed to room temperature
  5. stirringstirred overnight
  6. customThe reaction is quenched
  7. additionby pouring into an ice/1 N HCl mixture
  8. extractionis extracted three times with EtOAc
  9. dry with materialThe combined organic layers are dried over Na2SO4
  10. customthe solvent is removed under reduced pressure
  11. customto afford a residue that
  12. customis purified on silica gel chromatography
  13. washeluting with a linear gradient of 5% to 100% EtOAc in hexanes

Sources & evidence

ORD record
ord-8c97b1bc25de4d63843c6ccabe5575b8
Source dataset
uspto-grants-2012_10
Patent number
US08278441B2

Reaction notes

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