2,6-Dimethyl-4-phenyl-phenol → 3-(t-Butyldimethylsilyloxymethyl)-5-[3-[2,6-dimethyl-4-phenylphenoxy]-propyl]-isoxazole

HRID 2222225Notes

Reaction equation

HRID 2222225 reaction equation
[Si:1]([O:8][CH2:9][C:10]1[CH:14]=[C:13]([CH2:15][CH2:16][CH2:17][OH:18])[O:12][N:11]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH3:19][C:20]1[CH:25]=[C:24]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:23]=[C:22]([CH3:32])[C:21]=1[OH:33]>>[OH:8][CH2:9][C:10]1[CH:14]=[C:13]([CH2:15][CH2:16][CH2:17][O:18][C:21]2[C:20]([CH3:19])=[CH:25][C:24]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)=[CH:23][C:22]=2[CH3:32])[O:12][N:11]=1.[Si:1]([O:8][CH2:9][C:10]1[CH:14]=[C:13]([CH2:15][CH2:16][CH2:17][O:33][C:21]2[C:22]([CH3:32])=[CH:23][C:24]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[CH:25][C:20]=2[CH3:19])[O:12][N:11]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 97942002,6-Dimethyl-4-phenyl-phenolHCID 104233433-(t-Butyldimethylsilyloxymethyl)-5-(3-hydroxypropyl)isoxazole

Product 2

HCID 693066563-(t-Butyldimethylsilyloxymethyl)-5-[3-[2,6-dimethyl-4-phenylphenoxy]-propyl]-isoxazoleHCID 693066623-(Hydroxymethyl)-5-[3-[2,6-dimethyl-4-phenylphenoxy]-propyl]-isoxazole

Procedure

3-(Hydroxymethyl)-5-[3-[2,6-dimethyl-4-phenylphenoxy]-propyl]-isoxazole was prepared following procedures described in the literature; J. Med. Chem. (1994) 37 2421, thus 3-(t-butyldimethylsilyloxymethyl)-5-(3-hydroxypropyl)isoxazole (ibid.) and 2,6-dimethyl-4-phenyl-phenol were coupled by way of a Mitsunobu reaction to give the adduct, 3-(t-butyldimethylsilyloxymethyl)-5-[3-[2,6-dimethyl-4-phenylphenoxy]-propyl]-isoxazole in 82% yield. 1H nmr (CDCl3): δ=7.6-7.2 (m, 7H); 6.13 (s, 1); 4.75 (d, 2H); 3.86 (t, 2H); 3.07 (t, 2H); 2.33 (s, 6H); 2.23 (m, 2H) and 2.1 (t, OH). MS (ES): (M+H) 338.1748 (calc. C21H24NO3 338.1750). Removal of the silyloxy group under acidic hydrolysis gave the hydroxy compound, 3-(hydroxymethyl)-5-[3-[2,6-dimethyl-4-phenylphenoxy]-propyl]-isoxazole in 93% yield. 1H mm (CDCl3): δ=7.6-7.2 (m, 7H); 6.13 (s, 1H); 4.75 (d, 2H); 3.86 (t, 2H); 3.07 (t, 2H); 2.33 (s, 6H); 2.23 (m, 2H) and 2.1 (t, OH). MS (ES): (M+H) 338.1748 (calc. C21H24NO3 338.1750). Bromination of the hydroxy compound following the procedure of example 1 gave the bromomethyl compound, 3-(bromomethyl)-5-[3-[2,6-dimethyl-4-phenylphenoxy]-propyl]-isoxazole in 95% yield. 1H nmr (CDCl3): δ=7.6-7.2 (m, 7H); 6.17 (s, 1H); 4.41 (s, 2H); 3.86 (t, 2H); 3.07 (t, 2H); 2.33 (s, 6H) and 2.23 (m, 2H). MS(ES): (M+Na)+ 422.0725 (calc. C21H22BrNO2Na 422.0720).

Sources & evidence

ORD record
ord-252e01dcb8be456baac3b14a52c3e888
Source dataset
uspto-grants-2008_05
Patent number
US07371755B1

Reaction notes

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