4-Toluenesulfonyl chloride → (+/-)-(5-Chloro-7-methoxy-2-methyl-2,3-dihydro-1-benzofuran-2-yl)methyl 4-methylbenzenesulfonate

HRID 2116016Notes

Reaction equation

HRID 2116016 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([O:14][CH3:15])[C:5]2[O:9][C:8]([CH2:11][OH:12])([CH3:10])[CH2:7][C:6]=2[CH:13]=1.[C:16]1([CH3:26])[CH:21]=[CH:20][C:19]([S:22](Cl)(=[O:24])=[O:23])=[CH:18][CH:17]=1.C(N(C(C)C)CC)(C)C>CN(C)C1C=CN=CC=1>[CH3:26][C:16]1[CH:21]=[CH:20][C:19]([S:22]([O:12][CH2:11][C:8]2([CH3:10])[CH2:7][C:6]3[CH:13]=[C:2]([Cl:1])[CH:3]=[C:4]([O:14][CH3:15])[C:5]=3[O:9]2)(=[O:24])=[O:23])=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 68966493(+/-)-(5-Chloro-7-methoxy-2-methyl-2,3-dihydro-1-benzofuran-2-yl)methanol

Product 1

HCID 86599125(+/-)-(5-Chloro-7-methoxy-2-methyl-2,3-dihydro-1-benzofuran-2-yl)methyl 4-methylbenzenesulfonateYield 76.7%

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Procedure

Treatment of 4-chloro-2-methoxyphenol (15.00 g, 0.10 mol) with sodium hydride (4.4 g, 0.11 mol, 60 wt. %) and 3-chloro-2-methylpropene (12.00 g, 0.12 mol) generally according to the procedure described for Intermediate 13 provided 19.3 g (91%) of 4-chloro-2-methoxy-1-[(2-methylprop-2-enyl)oxy]benzene as a colorless oil. Treatment of the allyl ether in refluxing mesitylene generally according to the procedure described for Intermediate 8 afforded 15.5 g (78%) of 4-chloro-2-methoxy-6-(2-methylprop-2-enyl)phenol as a pale yellow oil. Treatment of 4-chloro-2-methoxy-6-(2-methylprop-2-enyl)phenol (10.00 g, 0.047 mol) with 3-chloroperoxybenzoic acid (20.00 g, 0.089 mol, 77%) followed by potassium carbonate (20.00 g, 0.145 mol) generally according to the Procedure described for Intermediate 9 provided 8.00 g (74%) of (±)-(5-chloro-7-methoxy-2-methyl-2,3-dihydro-1-benzofuran-2-yl)methanol as a light yellow oil. Treatment of (±)-(5-chloro-7-methoxy-2-methyl-2,3-dihydro-1-benzofuran-2-yl)methanol (10.8 g, 0.047 mol) with p-toluenesulfonyl chloride (13.5 g, 0.071 mol), diisopropylethylamine (12.15 g, 0.094 mol), and 4-(dimethylamino)pyridine (0.35 g, 2.83 mmol) generally according to the procedure described for Intermediate 45 gave 13.8 g (76%) of (±)-(5-chloro-7-methoxy-2-methyl-2,3-dihydro-1-benzofuran-2-yl)methyl 4-methylbenzenesulfonate as a white solid. mp 113-115° C.; Anal. calcd. for C18H19ClO5S: C, 56.47; H, 5.00. Found: C, 55.82; H, 4.94.

Sources & evidence

ORD record
ord-2597886a22514999b5d5be621103b471
Source dataset
uspto-grants-2008_10
Patent number
US07435837B2

Reaction notes

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