Triethylamine → HCID 58909332, compound

HRID 1991527Notes

Reaction equation

HRID 1991527 reaction equation
C(OC)(OC)(OC)C.[CH2:9]([O:16][C:17]1[CH:36]=[CH:35][C:20]([CH2:21][C@H:22]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[C@H:23](O)[CH2:24][OH:25])=[CH:19][C:18]=1[F:37])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(N(CC)CC)C.C(Br)(=O)C.[OH-].[K+]>C(Cl)Cl.CO.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>[CH2:9]([O:16][C:17]1[CH:36]=[CH:35][C:20]([CH2:21][C@H:22]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:31])([CH3:33])[CH3:32])[C@H:23]2[CH2:24][O:25]2)=[CH:19][C:18]=1[F:37])[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 10482Acetyl bromideHCID 14797Potassium HydroxideHCID 15050Trimethyl orthoacetateHCID 58909337HCID 58909337, compound

Product 1

HCID 58909332HCID 58909332, compoundYield 72.2%

Reagents, catalysts & solvents 3

HCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)CatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

Trimethyl orthoacetate (0.94 mL, 7.4 mmol) is added to a suspension of compound 16 (2.9 g, 7.2 mmol) in 30 mL of CH2Cl2 stirred under nitrogen. Pyridinium p-toluenesulfonate (18 mg, 0.07 mmol) is added and the resulting pale yellow solution is stirred for 30 min and then concentrated to a white solid. This solid is dissolved in 30 mL of CH2Cl2, triethylamine (0.10 mL, 0.72 mmol) is added, and the mixture, under nitrogen, is cooled in an ice bath. Freshly distilled acetyl bromide (0.55 mL, 7.4 mmol) is added dropwise over 3-4 min with stirring. After 1 h, the ice bath is removed and aqueous 1 N NaHCO3 and CH2Cl2 are added. The aqueous phase is extracted with additional CH2Cl2 and the combined organic phases are dried over MgSO4 and concentrated to a white solid. This solid is suspended in 25 mL of methanol and 6 mL of THF, and cooled in an ice bath, under nitrogen. Pulverized KOH (0.60 g, 11 mmol) in 6 mL of methanol is added all at once. After 15 min the ice bath is removed and the mixture is allowed to come to ambient temperature over 70 min. The mixture is concentrated and taken up in ethyl acetate and aqueous 1N KH2PO4. The organic phase is washed with 1N NaHCO3 and then brine, dried over Na2SO4, and concentrated. Chromatography over silica gel, eluting with 20% ethyl acetate and 5% to 10% CH2Cl2 in heptane affords 2.0 g (5.2 mmol, 72%) of compound 17 as a white solid: 1H NMR (CDCl3) δ 7.45-7.30 (m, 5H), 6.99-6.86 (m, 3H), 5.12 (s, 2H), 4.43 (br, 1H), 3.63 (br, 1H), 2.90 (m, 2H), 2.79 (m, 2H), 2.74 (m, 1H), 1.39 (s, 9H); MS (CI) m/z 410.3 (MNa+), 388.3 (MH+).

Workup

  1. stirringthe resulting pale yellow solution is stirred for 30 min
  2. concentrationconcentrated to a white solid
  3. dissolutionThis solid is dissolved in 30 mL of CH2Cl2
  4. temperaturethe mixture, under nitrogen, is cooled in an ice bath
  5. stirringwith stirring
  6. customthe ice bath is removed
  7. additionaqueous 1 N NaHCO3 and CH2Cl2 are added
  8. extractionThe aqueous phase is extracted with additional CH2Cl2
  9. dry with materialthe combined organic phases are dried over MgSO4
  10. concentrationconcentrated to a white solid
  11. temperature6 mL of THF, and cooled in an ice bath, under nitrogen
  12. customAfter 15 min the ice bath is removed
  13. waitto come to ambient temperature over 70 min
  14. concentrationThe mixture is concentrated
  15. washThe organic phase is washed with 1N NaHCO3
  16. dry with materialbrine, dried over Na2SO4
  17. concentrationconcentrated
  18. washChromatography over silica gel, eluting with 20% ethyl acetate and 5% to 10% CH2Cl2 in heptane

Sources & evidence

ORD record
ord-6c9635413f6b40b9a473fb41fdbee579
Source dataset
uspto-grants-2010_01
Patent number
US07645780B2

Reaction notes

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