Chloromethyl Methyl Ether → 2-Methoxymethoxy-6-methyl-4-(tetrahydro-pyran-2-yloxy)-benzaldehyde

HRID 1798149Notes

Reaction equation

HRID 1798149 reaction equation
[OH:1][C:2]1[CH:9]=[C:8]([O:10][CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)[CH:7]=[C:6]([CH3:17])[C:3]=1[CH:4]=[O:5].CCN(C(C)C)C(C)C.[CH2:27](Cl)[O:28][CH3:29]>C(Cl)Cl>[CH3:27][O:28][CH2:29][O:1][C:2]1[CH:9]=[C:8]([O:10][CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)[CH:7]=[C:6]([CH3:17])[C:3]=1[CH:4]=[O:5]

Participants

5

Reactant 3

HCID 7864Chloromethyl Methyl EtherHCID 81531DiisopropylethylamineHCID 10823699HCID 10823699, compound

Product 1

HCID 866539772-Methoxymethoxy-6-methyl-4-(tetrahydro-pyran-2-yloxy)-benzaldehydeYield 81.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-hydroxy-6-methyl-4-(tetrahydro-pyran-2-yloxy)-benzaldehyde (10.4 g, 44.0 mmol) in DCM (100 mL) at 0° C. was added DIPEA (11.5 mL, 66.0 mmol) followed by MOMCl (5.0 mL, 66.0 mmol). The reaction mixture was allowed to warm to room temperature and stirred for 6 hours. The mixture was concentrated in vacuo and the residue purified by silica gel flash column chromatography (hexane:EtOAc 70:30) to give 2-methoxymethoxy-6-methyl-4-(tetrahydro-pyran-2-yloxy)-benzaldehyde (10.0 g, 81%). 1H NMR (400 MHz, CDCl3): δ 10.52 (s, 1H), 6.71 (d, J=2.4 Hz, 1H), 6.55 (d, J=1.6 Hz, 1H), 5.51 (t, J=3.2 Hz, 1H), 5.25 (q, J=6.8 Hz, 2H), 3.87-3.81 (m, 1H), 3.65-3.61 (m, 1H), 3.51 (s, 3H), 2.57 (s, 3H), 2.04-1.58 (m, 6H). MS (ESI) m/z=281 [M+H]+.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customthe residue purified by silica gel flash column chromatography (hexane:EtOAc 70:30)

Sources & evidence

ORD record
ord-48aae3259d4d4c4288f156cba596a299
Source dataset
uspto-grants-2013_01
Patent number
US08343944B2

Reaction notes

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