Methyl pyruvate → HCID 18790148, compound

HRID 1107181Notes

Reaction equation

HRID 1107181 reaction equation
C([Li])CCC.[C:6]1([CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][S:17]([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)(=[O:19])=[O:18])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[C:28]([O:33][CH3:34])(=[O:32])[C:29]([CH3:31])=[O:30]>C1COCC1>[OH:30][C:29]([CH3:31])([CH:16]([S:17]([C:20]1[CH:21]=[CH:22][C:23]([O:26][CH3:27])=[CH:24][CH:25]=1)(=[O:19])=[O:18])[CH2:15][CH2:14][CH2:13][CH2:12][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[C:28]([O:33][CH3:34])=[O:32]

Participants

5

Reactant 3

HCID 11748Methyl pyruvateHCID 18790039HCID 18790039, compoundHCID 178418339Butyllithium

Product 1

HCID 18790148HCID 18790148, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of n-butyl lithium in hexanes (1.9 mL, 4.4 mmol) is added dropwise to a solution of 1-(5-phenylpentane-1-sulfonyl)-4-methoxybenzene (1.35 g, 4.24 mmol) in THF (15 mL) at -78° C. The reaction is stirred at -78° C. for 15 minutes, raised to -30° C. for 15 minutes and then returned to -78° C. This solution is then cannulated into a solution of methyl pyruvate (0.82 g, 7.2 mmol) in THF (5 mL) precooled to -78° C. After 15 minutes the reaction is slowly warmed to -30° C. and stirred 15 minutes before quenching with a solution of NH4Cl (15 mL). The reaction is partitioned between ether (150 mL) and water (50 mL), and the layers are separated. The ether layer is washed with brine (50 mL), dried (MgSO4) and concentrated in vacuo. The crude product is purified by gradient elution chromatography (silica, CH2Cl2 to 1% MeOH in CH2Cl2) to yield a diastereomeric mixture (2:3 ratio) of methyl 2-hydroxy-3-(4-methoxybenzenesulfonyl)-2-methyl-7-phenylheptanoate products (0.60 g, 35%). An analytical sample of each isomer is obtained by additional chromatography using identical conditions; upper isomer, methyl 2-hydroxy-3-(4-methoxybenzenesulfonyl)-2-methyl-7-phenylheptanoate: 1H NMR (300 MHz, CDCl3) δ 7.78 (d, J=8.7 Hz, 2H), 7.28-7.23 (m, 2H), 7.19-7.14 (m, 1H), 7.06 (d, J=7.6 Hz, 2H), 6.99-6.94 (m, 2H), 4.0-3.7 (br,1H), 3.87 (s, 3H), 3.78 (s, 3H), 3.34-3.30 (m, 1H), 2.45 (t, J=7.5 Hz, 2H), 1.98-1.75 (m, 2H), 1.61 (s, 3H), 1.48-1.38 (m, 2H), 1.29-1.10 (m, 2H); MS (FAB) m/e 421 (M+H)+ ; lower isomer methyl 2-hydroxy-3-(4-methoxybenzenesulfonyl)-2-methyl-7-phenylheptanoate: 1H NMR (300 MHz, CDCl3) δ 7.77-7.74 (m, 2H), 7.28-7.23 (m, 2H), 7.20-7.15 (m, 1H), 7.09 (d, J=7.6 Hz, 2H), 6.99-6.94 (m, 2H), 3.87 (s, 3H), 3.84 (s, 3H), 3.64 (bs, 1H), 3.52 (t, J=6.5 Hz, 1H), 2.51 (t, J=7.5 Hz, 2H), 1.92-1.86 (m, 2H), 1.52-1.33 (m, 4H), 1.41 (s, 3H); MS (FAB) m/e 421 (M+H)+.

Workup

  1. temperatureraised to -30° C. for 15 minutes
  2. customreturned to -78° C
  3. customprecooled to -78° C
  4. temperatureAfter 15 minutes the reaction is slowly warmed to -30° C.
  5. stirringstirred 15 minutes
  6. custombefore quenching with a solution of NH4Cl (15 mL)
  7. customThe reaction is partitioned between ether (150 mL) and water (50 mL)
  8. customthe layers are separated
  9. washThe ether layer is washed with brine (50 mL)
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated in vacuo
  12. customThe crude product is purified by gradient elution chromatography (silica, CH2Cl2 to 1% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-b5d414e2cf0f4b1ab03a7519511384f0
Source dataset
uspto-grants-2000_05
Patent number
US06057369

Reaction notes

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