Triethylsilane → 5-(4-[(4-phenoxybenzyl)oxy]methylphenyl)isothiazol-3(2H)-one 1,1-dioxide

HRID 724698Notes

Reaction equation

HRID 724698 reaction equation
[OH:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[S:13](=[O:15])(=[O:14])[NH:12][C:11](=[O:16])[CH:10]=2)=[CH:5][CH:4]=1.[O:17]([C:24]1[CH:31]=[CH:30][C:27]([CH:28]=O)=[CH:26][CH:25]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C([SiH](CC)CC)C>Cl.O1CCOCC1>[O:17]([C:24]1[CH:25]=[CH:26][C:27]([CH2:28][O:1][CH2:2][C:3]2[CH:4]=[CH:5][C:6]([C:9]3[S:13](=[O:15])(=[O:14])[NH:12][C:11](=[O:16])[CH:10]=3)=[CH:7][CH:8]=2)=[CH:30][CH:31]=1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

6

Reactant 3

HCID 12052Triethylsilane2×HCID 661394-PhenoxybenzaldehydeHCID 218788375-[4-(Hydroxymethyl)phenyl]isothiazol-3(2H)-one 1,1-dioxide

Product 1

HCID 218786685-(4-[(4-phenoxybenzyl)oxy]methylphenyl)isothiazol-3(2H)-one 1,1-dioxideYield 5%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolvent2×HCID 312751,4-DioxaneSolvent2×

Procedure

5-[4-(Hydroxymethyl)phenyl]isothiazol-3(2H)-one 1,1-dioxide (80 mg, 0.33 mmol) was suspended in 4 M hydrogen chloride in 1,4-dioxane (2.0 mL). 4-Phenoxybenzaldehyde (0.080 mL, 0.46 mmol) was added, followed 15 minutes later by triethylsilane (0.075 mL, 0.47 mmol). After stirring for 21 h, additional triethylsilane (0.050 mL, 0.31 mmol) was added, followed 3.5 h later by 4 M hydrogen chloride in 1,4-dioxane (1.0 mL, 4 mmol). The product was purified on a 50 mm Luna C18 column using a 20–100% acetonitrile in water gradient with 0.05% trifluoroacetic acid at 30 mL per minute over a 30 minute period. The product was lyophilized to give a white powder (7 mg, 5%). 1H NMR (400 MHz, CDCl3): δ 7.80 (d, J=8.4 Hz, 2H), 7.54 (d, J=8.6 Hz, 2H), 7.34 (m, 4H), 7.11 (t, J=1.2 Hz, 1H), 7.01 (m, 4H), 6.71 (s, 1H), 4.63 (s, 2H), 4.56 (s, 2H); LCMS found for C23H19NNaO5S (M+Na)+: m/z=444.0.

Workup

  1. customThe product was purified on a 50 mm Luna C18 column
  2. customover a 30 minute

Sources & evidence

ORD record
ord-86f8280aa67c4afdb66784b81afbe40b
Source dataset
uspto-grants-2006_11
Patent number
US07141596B2

Reaction notes

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