Chlorotrimethylsilane → HCID 53971920, compound

HRID 1635679Notes

Reaction equation

HRID 1635679 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C@H:8]([N:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][C:19]=3[O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH2:14][CH2:13]2)[CH2:9][CH2:10][OH:11])[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.Cl[Si](C)(C)C.ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl>ClCCl>[Br:1][C:2]1[CH:3]=[C:4]([C@H:8]([N:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][C:19]=3[O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH:14]=[CH:13]2)[CH2:9][CH2:10][OH:11])[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinoneHCID 8471TriethylamineHCID 53802110HCID 53802110, compound

Product 1

HCID 53971920HCID 53971920, compoundYield 80.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A stirred solution of (3R)-(−)-3-(3-bromophenyl)-3-(7-benzyloxyindolin-1-yl)propan-1-ol (1.0 g, 2.28 mmol) in dry dichloromethane (30.0 ml) under nitrogen at 5° C. was treated with triethylamine (0.52 ml, 3.77 mmol) followed by chlorotrimethylsilane (0.32 ml, 2.52 mmol) dropwise. The resulting suspension was stirred at room temperature for 20 min, treated with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (0.57 g, 2.52 mmol) and stirred at room temperature until the reaction was judged to be complete from TLC inspection (˜30 min). The solvent was removed by evaporation, the residue was taken up in ethyl acetate (200 ml), washed with 2M aqueous sodium hydroxide (3×100 ml), brine (100 ml) and 2M aqueous hydrochloric acid (2×100 ml). Evaporation of the dried organic extracts (Na2SO4) gave a yellow/brown oil. Column chromatography (ethyl acetate-light petroleum (b.p. 40-60° C.), 1:4) gave the title compound as a yellow oil (0.80 g, 80%). [α]D26 −157 (c=0.014 gml−1, CHCl3); νmax (thin film)/cm−1 3418.5 (br. OH), 3064.5, 3033.5, 2935.5, 2879.0, 1593.5, 1570.5; δH (270 MHz) 2.35 (2H, m, 2×2-H); 3.50 (2H, m, 2×1-H); 5.13 (2H, q, CH2Ph, 2J=11.1 Hz); 6.6 (m, 2H, 3-H, indole 3-H); 6.72 (1H, dd, indole 6-H, Jo=7.6 Hz, Jm=0.7 Hz); 6.90 (1H, dd, indole 4-H, Jo=8.3 Hz, Jm=0.8 Hz); 7.00 (2H, m, indole 5-H, 5′-H); 7.15 (1H, d, indole 2-H, 3J2,3=3.0 Hz); 7.19-7.40 (8H, m, 8ArH). δC (67.8 MHz) 38.4 (2-C); 56.4 (3-C); 59.3 (1-C); 70.7 (PhCH2); 103.2 (indole 3-C); 104.3 (indole 6-C); 114.3 (indole 4-C); 120.1 (indole 5-C); 122.5 (3′-C); 125.0 (indole 2-C); 131.8 (1′-C); 136.4 (benzyl ipso-C); 144.9 (indole 7a-C); 146.5(indole 7-C). The remaining signals lie between 126.5-130.7 ppm and cannot be assigned with any certainty.

Workup

  1. stirringstirred at room temperature until the reaction
  2. customto be complete from TLC inspection (˜30 min)
  3. customThe solvent was removed by evaporation
  4. washwashed with 2M aqueous sodium hydroxide (3×100 ml), brine (100 ml) and 2M aqueous hydrochloric acid (2×100 ml)
  5. customEvaporation of the dried organic extracts (Na2SO4)
  6. customgave a yellow/brown oil

Sources & evidence

ORD record
ord-9e0b938aeee747b08e6e42daaedf2379
Source dataset
uspto-grants-2003_01
Patent number
US06509476B1

Reaction notes

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