Triethylamine → Ethyl 5-((1R,2S)-2-((tert-butyldimethylsilyl)oxy)-1-hydroxypropyl)-4-methylisoxazole-3-carboxylate

HRID 1478193Notes

Reaction equation

HRID 1478193 reaction equation
[C:1]([Si:5](Cl)([CH3:7])[CH3:6])([CH3:4])([CH3:3])[CH3:2].[OH:9][C@@H:10]([C:14]1[O:18][N:17]=[C:16]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:15]=1[CH3:24])[C@@H:11]([OH:13])[CH3:12].C(N(CC)CC)C>CN(C)C1C=CN=CC=1.CN(C=O)C>[Si:5]([O:13][C@@H:11]([CH3:12])[C@H:10]([C:14]1[O:18][N:17]=[C:16]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:15]=1[CH3:24])[OH:9])([C:1]([CH3:4])([CH3:3])[CH3:2])([CH3:7])[CH3:6]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 28928tert-Butyldimethylsilyl chlorideHCID 118511095ethyl 5-((1R,2S)-1,2-dihydroxypropyl)-4-methylisoxazole-3-carboxylate2×

Product 1

HCID 125496410Ethyl 5-((1R,2S)-2-((tert-butyldimethylsilyl)oxy)-1-hydroxypropyl)-4-methylisoxazole-3-carboxylate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

tertbutyldimethylsilyl chloride (6.3 g, 41.5 mmol) was added portionwise to ethyl 5-((1R,2S)-1,2-dihydroxypropyl)-4-methylisoxazole-3-carboxylate (Intermediate B)(8.65 g, 37.7 mmol), 4-dimethylaminopyridine (1.38 g, 11.32 mmol) and triethylamine (5.80 mL,) in DMF (100 mL) at 0° C. and the reaction was allowed to warm to room temperature. After 18 h the reaction was partitioned between EtOAc and brine, washed with saturated aqueous ammonium chloride, brine, dried over Na2SO4 and concentrated under reduced pressure. The crude material was adsorbed onto silica and purification by chromatography eluting with 15% EtOAc in iso-hexane afforded the title compound;

Workup

  1. customAfter 18 h the reaction was partitioned between EtOAc and brine
  2. washwashed with saturated aqueous ammonium chloride, brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe crude material was adsorbed onto silica and purification by chromatography
  6. washeluting with 15% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-d6d41c7093424988b8129d91e765de47
Source dataset
uspto-grants-2016_08
Patent number
US09403810B2

Reaction notes

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