Hydrochloric Acid → HCID 54045028, compound

HRID 2269325Notes

Reaction equation

HRID 2269325 reaction equation
[CH:1](NC(C)C)(C)[CH3:2].C([Li])CCC.[C:13]([O:17][C:18](=[O:46])[CH:19]([NH:27][S:28]([C:31]1[CH:36]=[CH:35][C:34]([O:37][CH2:38][C:39]2[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=2)=[CH:33][CH:32]=1)(=[O:30])=[O:29])CCCC(=O)CC)([CH3:16])([CH3:15])[CH3:14].Cl.[CH2:48]1[CH2:52][O:51][CH2:50][CH2:49]1>>[C:13]([O:17][C:18]([CH:19]1[C:52]([OH:51])([CH2:1][CH3:2])[CH2:48][CH2:49][CH2:50][N:27]1[S:28]([C:31]1[CH:36]=[CH:35][C:34]([O:37][CH2:38][C:39]2[CH:40]=[CH:41][C:42]([F:45])=[CH:43][CH:44]=2)=[CH:33][CH:32]=1)(=[O:30])=[O:29])=[O:46])([CH3:14])([CH3:16])[CH3:15]

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 8028Tetrahydrofuran2×HCID 54066264HCID 54066264, compoundHCID 178418339Butyllithium

Product 1

HCID 54045028HCID 54045028, compound

Procedure

To a solution of diisopropylamine (0.35 mL, 2.5 mmol) in 10 mL of THF at −78° C. was added n-butyllithium. The mixture was warmed to room temperature and stirred for 20 min. After cooling to −78° C., a solution of 2-[4-(4-fluoro-benzyloxy)-benzenesulfonylamino]-6-oxo-octanoic acid tert-butyl ester (1.0 g, 2.1 mmol) in 2.5 mL of THF was added dropwise. The mixture was warmed to room temperature and stirred for 3 h. After acidifying with 1M HCl, the mixture was extracted 2× into ethyl acetate, and the combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. Purification of the residue by radial chromatography (1% acetone-CH2Cl2, 2 mm plate) afforded ca. 0.37 g of the (2R,3S) diastereomer and 0.09 g of the (2R,3R) diastereomer of 1-[4-(4-fluoro-benzyloxy)-benzenesulfonyl]-3-hydroxy-3-ethyl-piperidine-2-carboxylic acid tert-butyl ester as colorless syrups:

Workup

  1. temperatureAfter cooling to −78° C.
  2. temperatureThe mixture was warmed to room temperature
  3. stirringstirred for 3 h
  4. extractionthe mixture was extracted 2× into ethyl acetate
  5. dry with materialthe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification of the residue by radial chromatography (1% acetone-CH2Cl2, 2 mm plate)

Sources & evidence

ORD record
ord-ef5b742482ad4d53bc1801ff8ad8be1c
Source dataset
uspto-grants-2001_12
Patent number
US06329397B1

Reaction notes

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