Hydroxyamine hydrochloride → (S)-5-(((tert-Butyldiphenylsilyl)oxy)methyl)-3-(pyrrolidin-2-yl)isoxazole

HRID 710034Notes

Reaction equation

HRID 710034 reaction equation
[Si:1]([O:18][CH2:19][C:20]#[C:21][C:22]([C@@H:24]1[CH2:28][CH2:27][CH2:26][N:25]1C(OC(C)(C)C)=O)=O)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[NH2:37][OH:38].C(=O)(O)[O-].[Na+]>CCO>[Si:1]([O:18][CH2:19][C:20]1[O:38][N:37]=[C:22]([C@@H:24]2[CH2:28][CH2:27][CH2:26][NH:25]2)[CH:21]=1)([C:14]([CH3:17])([CH3:15])[CH3:16])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 443297Hydroxyamine hydrochlorideHCID 516892Sodium BicarbonateHCID 86706745(S)-t-Butyl 2-(4-((tert-butyldiphenylsilyl)oxy)but-2-ynoyl)pyrrolidine-1-carboxylate

Product 1

HCID 86706746(S)-5-(((tert-Butyldiphenylsilyl)oxy)methyl)-3-(pyrrolidin-2-yl)isoxazoleYield 40.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To an EtOH (10 mL) solution of the compound (492 mg) obtained in Example 3-(1), hydroxylamine hydrochloride (139 mg) was added and the mixture was heated under reflux for 17 hours. To the reaction mixture, saturated aqueous sodium bicarbonate (50 ml) was added and the organic layer extracted with AcOEt was dried (MgSO4), filtered and concentrated to give a crude product, which was further purified by neutral silica gel chromatography (AcOEt→MeOH/CHCl3) to give the titled compound (163 mg, brown oil.)

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 17 hours
  3. extractionthe organic layer extracted with AcOEt
  4. dry with materialwas dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a crude product, which
  8. customwas further purified by neutral silica gel chromatography (AcOEt→MeOH/CHCl3)

Sources & evidence

ORD record
ord-eba761ef9d36438fb0106b7e7c3a4a61
Source dataset
uspto-grants-2015_11
Patent number
US09181229B2

Reaction notes

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