2-Chloromethyl 2-(trimethylsilyl)ethyl ether → HCID 68182961, compound

HRID 1615582Notes

Reaction equation

HRID 1615582 reaction equation
[Cl:1][C:2]1[S:10][C:9]2[S:8](=[O:12])(=[O:11])[NH:7][CH2:6][C:5]([C:14]3[CH:23]=[CH:22][C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[CH:15]=3)([OH:13])[C:4]=2[CH:3]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[CH3:34][Si:35]([CH3:42])([CH3:41])[CH2:36][CH2:37][O:38][CH2:39]Cl>C1COCC1>[Cl:1][C:2]1[S:10][C:9]2[S:8](=[O:12])(=[O:11])[N:7]([CH2:39][O:38][CH2:37][CH2:36][Si:35]([CH3:42])([CH3:41])[CH3:34])[CH2:6][C:5]([C:14]3[CH:23]=[CH:22][C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[CH:15]=3)([OH:13])[C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 2733832Lithium HexamethyldisilazideHCID 68182946HCID 68182946, compound

Product 1

HCID 68182961HCID 68182961, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 6-chloro-4-(2-naphthyl)-3,4-dihydro-2H-thieno[3,2-e][1,2]thiazin-4-ol 1,1-dioxide (0.235 g, 0.642 mmol) in THF (5.2 mL) at −78° C. was added 1.00 M Lithium hexamethyldisilazide in THF (0.771 mL, 0.771 mmol). The reaction mixture was stirred at −78° C. for 30 min, and [β-(trimethylsilyl)ethoxy]methyl chloride (0.341 mL, 1.93 mmol) was added at the same temperature. The mixture was stirred for 1 h at −78° C. and raised to rt. After stirring at rt for 30 min, the mixture was quenched by sat. NH4Cl, extracted with EA, dried and evaporated. The residue was purified by Isco silica gel chromatography (24 g cartridge), EA in hex, 0-30% using solid load to give the title compound (0.140 g, 42%). LCMS (FA) ES−: 494, 496. 1H NMR (400 MHz, DMSO) δ 7.95-7.92 (m, 4H), 7.55-7.52 (m, 2H), 7.32-7.29 (m, 1H), 6.77 (s, 1H), 6.74 (s, 1H), 4.91 (d, 1H), 4.64 (d, 1H), 4.20 (d, 1H), 3.95 (d, 1H), 3.52-3.47 (m, 2H), 0.85-0.76 (m, 2H), −0.05 (s, 9H).

Workup

  1. stirringThe mixture was stirred for 1 h at −78° C.
  2. temperatureraised to rt
  3. stirringAfter stirring at rt for 30 min
  4. customthe mixture was quenched by sat. NH4Cl
  5. extractionextracted with EA
  6. customdried
  7. customevaporated
  8. customThe residue was purified by Isco silica gel chromatography (24 g cartridge), EA in hex, 0-30%

Sources & evidence

ORD record
ord-9cb41fca0f854a169276c3df4c90c1f8
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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