4-Methoxybenzaldehyde → HCID 69443985, compound

HRID 1892014Notes

Reaction equation

HRID 1892014 reaction equation
CO[C:3]1[CH:4]=[CH:5][C:6]([CH:9]=O)=[CH:7][CH:8]=1.[CH3:11][OH:12].C(Cl)(Cl)Cl>[N+]([O-])([O-])=O.[Ag+].C(Cl)(Cl)Cl>[C:6]([C@H:9]1[C@:6]([CH3:9])([CH:7]=[CH2:8])[CH2:5][CH2:4][C@@H:3]([C:3]([CH3:4])=[CH2:8])[C@@H:11]1[OH:12])([CH3:7])=[CH2:5]

Participants

5

Reactant 2

HCID 312444-Methoxybenzaldehyde2×HCID 21584188Chloroform methanol

Product 1

HCID 69443985HCID 69443985, compound

Reagents, catalysts & solvents 2

HCID 24470Silver NitrateCatalystHCID 6212ChloroformSolvent

Procedure

Diethylaluminum chloride (210 ul, 1.8 M in toluene, 0.379 mmol, 1.1 equivalent) was added dropwise to a solution of ##STR4c## (76 mg, 0.344 mmol, 1.0 equivalent) in dry dichloromethane (10 ml) at −78 C. Agter 1.5 h, triethylamine (500 ul) was added, the cooling bath was removed, and the solution was added to a mixture of saturated NaHCO3 (20 ml) and dichloromethane (2×20 ml), and the organic fractions were combined, dried (MgSO4), and concentrated in vacuo. Flash chromatography (15 g of SiO2; eluent, 4% EtOAc-hexanes; product, fractions 11-23; 10 ml/fraction) afforded a 96:4 mixture of ##STR5a## and a minor diastereomer (70.1 mg, 0.318 mmol, 92% yield): Rf starting material, 0.58; product, 0.41 (5:1 hexanes-EtOAc, anisaldehyde). The diastereomeric mixture was separated by AgNO3-impregnated radial chromatography (2 mm plate; eluent, 5:1 EtOAc-hexanes; product, fractions 10-33; 3 ml/fraction) followed by passage through silica gel (10 g; 150 ml of 4% EtOAc-hexanes) to afford pure ##STR5a## (88% yield) as a clear oil: AgNO3-impregnated TLC: Rf ##STR5a##, 0.08; minor, 0.17 (12% MeOH—CHCl3; anisaldehyde); [α]23D+17.8° (c=0.91, CHCl3); FTIR (film) 3566, 3486, 2969, 2931, 1639, 1454, 1375, 1004, 910, 889 cm-1; sup.1 H NMR (500 MHz, CDCl3) δ 5.78 (dd, 1H, J=10.9, 17.4), 5.06 (s, 1H), 4.88-4.92 (m, 4H), 4.76 (s, 1H), 3.77 (t, 1H, J=10.4), 2.08 (dt, 1H, J=4.8, 10.8), 1.98 (d, 1H, J=10.4), 1.90 (bs, 1H), 1.80 (s, 3H), 1.79 (s, 3H), 1.51-1.66 (m, 3H), 1.42 (dt, 1H, J=3.1, 13.0), 1.06 (s, 3H); sup.13 C NMR (101 MHz, CDCl3) d 148.9, 147.1, 144.2, 114.1, 112.2, 110.3, 69.3, 59.7, 53.7, 41.3, 39.0, 26.2, 25.0, 19.5, 18.1; HRMS (EI, Pos) m/z calculated for [C15H24O]+220.1827, found 220.1826.

Workup

  1. additiona 96:4 mixture of ##STR5a## and a minor diastereomer (70.1 mg, 0.318 mmol, 92% yield)
  2. customThe diastereomeric mixture was separated by AgNO3-
  3. customto afford pure ##STR5a## (88% yield) as a clear oil

Sources & evidence

ORD record
ord-3440e4dff90c4a0e867b2de911e25766
Source dataset
uspto-grants-2013_08
Patent number
US08507562B2

Reaction notes

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