Sodium hydride → HCID 66686931, compound

HRID 1471419Notes

Reaction equation

HRID 1471419 reaction equation
CS(Cl)(=O)=O.[CH2:6]([O:13][C@@H:14]1[C@@H:18]([CH2:19][O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[O:17][C@@H:16]([N:28]2[CH:33]=[CH:32][C:31](=[O:34])[NH:30][C:29]2=[O:35])[C@@:15]1([OH:39])[CH2:36][CH2:37]O)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[H-].[Na+].[NH4+].[Cl-]>N1C=CC=CC=1.C(Cl)Cl.CO>[CH2:21]([O:20][C@H:19]1[C@@:15]2([O:39][CH2:37][CH2:36]2)[C@H:16]([N:28]2[CH:33]=[CH:32][C:31](=[O:34])[NH:30][C:29]2=[O:35])[O:17][C@@H:18]1[CH2:14][O:13][CH2:6][C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 31297Methanesulfonyl chloride2×HCID 66686569HCID 66686569, compound

Product 1

HCID 66686931HCID 66686931, compoundYield 79%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

Methanesulfonyl chloride (0.800 mL, 10.34 mmol) was added to 8 (4.32 g, 9.22 mmol) in dry pyridine (100 mL). After 1 hour and 15 minutes, 0.1 equivalents more methane-sulfonyl chloride was added and the mixture was further stirred at room temperature for 45 minutes. Then, a small amount of methanol was added and the mixture was evaporated to dryness. The residue was dissolved in ethyl acetate (100 mL) and washed with saturated NaHCO3 (2×50 mL). The combined aqueous layer was extracted with ethyl acetate. The combined organic layer was then dried over Na2SO4 and concentrated in vacuo. The obtained residue was dissolved in dry THF and 95% NaH (932 mg, 36.9 mmol) was added at once at room temperature. After stirring for 2 hours at room temperature, the reaction mixture was poured on a saturated aqueous solution of NH4Cl (30 mL) followed by addition of CH2Cl2 (250 mL). The separated organic layer was washed with saturated aqueous NaHCO3 (2×100 mL) and the combined aqueous layer was extracted with CH2Cl2 (250 mL). The combined organic layer was dried (Na2SO4), filtered and evaporated to dryness under reduced pressure. The residue obtained was purified by column chromatography eluting first with heptane, then with ethyl acetate to afford 9 (3.27 g, 79%) as a foam. HPLC Condition A, Rt: 2.33 min, m/z=451 (M+H)+. 1H NMR (400 MHz, CDCl3) δ ppm 2.20-2.38 (m, 1 H) 2.38-2.52 (m, 1 H) 3.62-3.73 (m, 1 H) 3.89-4.13 (m, 3 H) 4.38-4.56 (m, 3 H) 4.56-4.68 (m, 1 H) 4.70-4.88 (m, 2 H) 5.25 (d, J=8.00 Hz, 1 H) 6.25 (s, 1 H) 7.18-7.47 (m, 10 H) 7.87 (d, J=8.20 Hz, 1 H) 8.90 (br. s., 1 H)

Workup

  1. customthe mixture was evaporated to dryness
  2. dissolutionThe residue was dissolved in ethyl acetate (100 mL)
  3. washwashed with saturated NaHCO3 (2×50 mL)
  4. extractionThe combined aqueous layer was extracted with ethyl acetate
  5. dry with materialThe combined organic layer was then dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. dissolutionThe obtained residue was dissolved in dry THF
  8. stirringAfter stirring for 2 hours at room temperature
  9. washThe separated organic layer was washed with saturated aqueous NaHCO3 (2×100 mL)
  10. extractionthe combined aqueous layer was extracted with CH2Cl2 (250 mL)
  11. dry with materialThe combined organic layer was dried (Na2SO4)
  12. filtrationfiltered
  13. customevaporated to dryness under reduced pressure
  14. customThe residue obtained
  15. customwas purified by column chromatography
  16. washeluting first with heptane

Sources & evidence

ORD record
ord-efe7ff9d902d4bc096c3a21bc0448dee
Source dataset
uspto-grants-2015_04
Patent number
US09012428B2

Reaction notes

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