Hydrochloric Acid → HCID 21463004, compound

HRID 1940542Notes

Reaction equation

HRID 1940542 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:6]=[CH:5]2.C([Li])(C)(C)C.[C:26]([N:29]1[CH2:34][CH2:33][C:32](=[O:35])[CH2:31][CH2:30]1)(=[O:28])[CH3:27].Cl>O1CCCC1>[OH:35][C:32]1([C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[N:7]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:12]([CH3:13])[CH3:14])[CH:15]([CH3:16])[CH3:17])[CH:6]=[CH:5]3)[CH2:33][CH2:34][N:29]([C:26](=[O:28])[CH3:27])[CH2:30][CH2:31]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 122563N-Acetyl-4-piperidoneHCID 27946525-Bromo-1-(triisopropylsilyl)-1H-indoleHCID 178418306HCID 178418306, compound

Product 1

HCID 21463004HCID 21463004, compoundYield 21%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

5-Bromo-1-triisopropylsilyl-1H-indole (13.7 g, 38.9 mmol) in tetrahydrofuran (250 ml) at -78° C. was treated with t-butyllithium (45.8 ml, 77.8 mmol, 1.7M solution in pentanes) and stirred at this temperature for 15 minutes. The yellow solution formed was added to 1-acetyl-4-piperidone (5.49 g, 38.9 mmol) in tetrahydrofuran (250 ml) at -78° C., and the mixture allowed to warm to room temperature. Hydrochloric acid (40 ml, 1M) was added and the mixture extracted with ethyl acetate (2×500 ml). The extracts were combined, dried (MgSO4) and concentrated. The crude product was purified by flash chromatography using ethyl acetate as eluant, to give 1-[4-hydroxy-4-(1-triisopropylsilyl-1H-indol-5-yl)piperidin-1-yl]ethanone (3.39 g, 21%) as a white solid; δH (DMSO-d6) 1.10 (18H, d, J 7.9 Hz, 6×CH3), 1.70 (3H, m, 3×CH), 2.00 (2H, m, piperidinyl H), 2.05 (3H, s, COCH3), 2.45 (1H, m, piperidinyl H), 3.00 (1H, m, piperidinyl H), 3.30 (1H, m, piperidinyl H), 3.50 (1H, m, piperidinyl H), 3.70 (1H, m, piperidinyl H), 4.30 (1H, m, piperidinyl H), 5.00 (1H, s, OH), 6.60 (1H, d, J 2.8 Hz, ArH), 7.30 (1H, d, J 7.8 Hz, ArH), 7.35 (1H, d, J 2.2 Hz, ArH), 7.50 (1H, d, J 7.9 Hz, ArH), and 7.70 (1H, s, ArH).

Workup

  1. customThe yellow solution formed
  2. extractionthe mixture extracted with ethyl acetate (2×500 ml)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-bb6a0de28fb842538b85f58fef5f9771
Source dataset
uspto-grants-1997_12
Patent number
US05700809

Reaction notes

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