Hydrochloric Acid → HCID 89519566, compound

HRID 1912371Notes

Reaction equation

HRID 1912371 reaction equation
CON(C)[C:4](=O)[C@@H:5]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:6][C:7]1[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3].Cl.[CH3:30][S:31]([CH2:34]P(=O)(OCC)OCC)(=[O:33])=[O:32].[H-].[Na+]>C1COCC1.CC(C)=O>[CH3:30][S:31](/[CH:34]=[CH:4]/[C@@H:5]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:17])([CH3:18])[CH3:19])[CH2:6][C:7]1[CH:8]=[CH:9][N:10]=[CH:11][CH:12]=1)(=[O:33])=[O:32]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 533797Diethyl (methanesulfonylmethyl)phosphonateHCID 21226445Aluminium lithium hydrideHCID 54402107HCID 54402107, compound

Product 1

HCID 89519566HCID 89519566, compound

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

Weinreb amide 76 (0.33 g, 1.08 mmol) was dissolved in THF (15 mL), put under an argon atmosphere and cooled to 0° C. LiAlH4 (1.5 eq., 1.68 mmol, 1.68 mL of a 1 M solution in THF) was added slowly and the mixture was stirred at 0° C. for 1 hour after which TLC analysis indicated complete conversion of the starting compound. 0.1 M aq. HCl (1 mL) was slowly added and the mixture was stirred vigorously for 5 minutes. The organic layer was extracted with sat. aq. NaHCO3 (2×) and brine, dried over MgSO4 and concentrated under reduced pressure. Diethyl ((methylsulfonyl)methyl)phosphonate (1.5 eq., 1.68 mmol, 0.39 g) was dissolved in THF (20 mL) and cooled to 0° C. under an argon atmosphere. NaH (1.3 eq., 1.46 mmol, 58.0 mg, 60% w/w in mineral oil) was slowly added and the mixture was stirred at 0° C. for 30 minutes. Next, the freshly obtained aldehyde (in THF (2 mL)) was slowly added and the mixture was stirred for 2 hours while slowly warming it to room temperature. After this time, TLC analysis indicated complete conversion of the aldehyde. The reaction was quenched by addition of 1 M aq. HCl (1 mL) after which the mixture was diluted with EtOAc and extracted with sat. aq. NaHCO3 (2×) and brine, dried over MgSO4 and concentrated under reduced pressure. The title compound was obtained after column chromatography (40%->80% Acetone/PE) as a colorless solid (yield: 117 mg, 0.36 mmol, 32%). 1H NMR (400 MHz, CDCl3): δ=8.50 (d, J=5.28 Hz, 2H), 7.15 (d, J=5.90 Hz, 2H), 6.92 (dd, J=15.10, 4.76 Hz, 1H), 6.53 (d, J=15.10 Hz, 1H), 5.56 (d, J=8.99 Hz, 1H), 4.80-4.72 (m, 1H), 3.02-2.84 (m, 2H), 2.93 (s, 3H), 1.39 (s, 9H) ppm. 13C NMR (100 MHz, CDCl3): δ=154.87, 149.59, 146.40, 145.41, 130.04, 124.51, 80.10, 51.10, 42.58, 39.48, 28.06 ppm. [α]D23=−6.0 (c=1, MeOH). HRMS: calcd. for C15H22N2O4S [M+H]+327.13730. found 327.13741.

Workup

  1. stirringthe mixture was stirred vigorously for 5 minutes
  2. extractionThe organic layer was extracted with sat. aq. NaHCO3 (2×) and brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. temperaturecooled to 0° C. under an argon atmosphere
  6. stirringthe mixture was stirred at 0° C. for 30 minutes
  7. stirringthe mixture was stirred for 2 hours
  8. temperaturewhile slowly warming it to room temperature
  9. customThe reaction was quenched by addition of 1 M aq. HCl (1 mL) after which the mixture
  10. additionwas diluted with EtOAc
  11. extractionextracted with sat. aq. NaHCO3 (2×) and brine
  12. dry with materialdried over MgSO4
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-9934c870918f4b3482ecd7d1be92683e
Source dataset
uspto-grants-2013_12
Patent number
US08609610B2

Reaction notes

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