Acetyl chloride → 5-{2-[2-(3-Chloro-phenyl)-2-hydroxy-ethylamino]-propyl}-benzo[1,3]dioxole-2,2-dicarboxylic acid bis-trimethylsilanylmethyl ester

HRID 1416746Notes

Reaction equation

HRID 1416746 reaction equation
C(Cl)(=O)C.[CH3:5][Si:6]([CH2:9][OH:10])([CH3:8])[CH3:7].[Cl:11][C:12]1[CH:13]=[C:14]([CH:18]([OH:39])[CH2:19][NH:20][CH:21]([CH3:38])[CH2:22][C:23]2[CH:37]=[CH:36][C:26]3[O:27][C:28]([C:33]([OH:35])=[O:34])([C:30](O)=[O:31])[O:29][C:25]=3[CH:24]=2)[CH:15]=[CH:16][CH:17]=1>C(=O)(O)[O-].[Na+]>[CH3:5][Si:6]([CH:9]([O:10][C:30]([C:28]1([C:33]([OH:35])=[O:34])[O:27][C:26]2[CH:36]=[CH:37][C:23]([CH2:22][CH:21]([NH:20][CH2:19][CH:18]([C:14]3[CH:15]=[CH:16][CH:17]=[C:12]([Cl:11])[CH:13]=3)[OH:39])[CH3:38])=[CH:24][C:25]=2[O:29]1)=[O:31])[Si:6]([CH3:8])([CH3:7])[CH3:5])([CH3:8])[CH3:7]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 766921-(Trimethylsilyl)methanolHCID 42813555-{2-[2-(3-Chloro-phenyl)-2-hydroxy-ethylamino]-propyl}-benzo[1,3]dioxole-2,2-dicarboxylic acid

Product 1

HCID 545322895-{2-[2-(3-Chloro-phenyl)-2-hydroxy-ethylamino]-propyl}-benzo[1,3]dioxole-2,2-dicarboxylic acid bis-trimethylsilanylmethyl esterYield 78.6%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Procedure

Acetyl chloride (0.59 g, 7.5 mmol) was added to trimethylsilylmethanol (4.03 g, 37.5 mmol) with stirring at room temperature. After 0.5 h, 5-{2-[2-(3-chloro-phenyl)-2-hydroxy-ethylamino]-propyl}-benzo[1,3]dioxole-2,2-dicarboxylic acid (1.05 g, 2.5 mmol) was added in portions. The resulting solution was stirred for 3 days, and then treated with 50 ml of 50% sodium bicarbonate solution, followed by extraction with ethyl acetate (50 ml). The organic extract was dried over anhydrous sodium sulfate, filtered, and evaporated. The residue was passed through a pad of silica gel, eluting with hexanes, and ether-hexanes/1:1 until no more trimethylsilylmethanol could be detected. The filter pad was then eluted with ethyl acetate, and the solvent was evaporated to give 1.14 g of the desired product as a colorless gum. Conversion to the HCl salt yielded 1.16 g of white foam; 1H NMR (CDCl3) δ 0.06 (s, 18H), 1.33 (d, J=6.5 Hz, 3H), 2.80 (m, 1H), 3.15 (m, 1H), 3.20 (m, 1H), 3.48 (m, 2H), 4.014 (s, 2H), 4.015 (s, 2H), 5.45 (bd, J=9.7 Hz, 1H), 5.60 (bs, 1H), 6.80 (m, 3H), 7.25 (m, 2H), 7.45 (s, 1H), 8.70 (bs, 1H), 10.10 (bs, 1H); IR (KBr): 1763 cm-1 (C=O); MS (ES) m/z 594 (MH+); [α]D25 -23° (c, 1.0, CHCl3). Anal. Calcd. for C28H40ClNO7Si2 ·HCl: C, 53.32; H, 6.39; N, 2.22; Cl, 11.24; Si, 8.91. Found: C, 52.65; H, 6.70; N, 2.11; Cl, 11.47; Si, 9.00.

Workup

  1. stirringThe resulting solution was stirred for 3 days
  2. extractionfollowed by extraction with ethyl acetate (50 ml)
  3. extractionThe organic extract
  4. dry with materialwas dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. washeluting with hexanes, and ether-hexanes/1:1 until no more trimethylsilylmethanol
  8. washThe filter pad was then eluted with ethyl acetate
  9. customthe solvent was evaporated

Sources & evidence

ORD record
ord-fe2973fa935d40a4badf95d9099f26ba
Source dataset
uspto-grants-1999_06
Patent number
US05914339

Reaction notes

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