Triethylborane → {(S)-1-[hydroxy-(5-thiophen-2-yl-oxazol-2-yl)-methyl]-propyl}-carbamic acid tert-butyl ester

HRID 1455576Notes

Reaction equation

HRID 1455576 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[O:10][CH:9]=[N:8][CH:7]=1.C(B(CC)CC)C.C([Li])CCC.[C:23]([O:27][C:28](=[O:35])[NH:29][CH:30]([CH:33]=[O:34])[CH2:31][CH3:32])([CH3:26])([CH3:25])[CH3:24]>C1COCC1>[C:23]([O:27][C:28](=[O:35])[NH:29][C@H:30]([CH:33]([OH:34])[C:9]1[O:10][C:6]([C:2]2[S:1][CH:5]=[CH:4][CH:3]=2)=[CH:7][N:8]=1)[CH2:31][CH3:32])([CH3:24])([CH3:25])[CH3:26]

Participants

6

Reactant 4

HCID 7357TriethylboraneHCID 27972085-(Thiophen-2-yl)-1,3-oxazoleHCID 11286906tert-butyl N-(1-oxobutan-2-yl)carbamateHCID 178418339Butyllithium

Product 1

HCID 57535376{(S)-1-[hydroxy-(5-thiophen-2-yl-oxazol-2-yl)-methyl]-propyl}-carbamic acid tert-butyl esterYield 38.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 5-thiophen-2-yl-oxazole (0.85 g, 5.62 mmol) in dry THF (4 mL) is added triethylborane (1.0 M in THF, 5.62 mmol, 5.62 mL). The mixture is stirred at room temperature for 45 min, then cooled to −78° C. and n-butyl lithium (1.6 M in hexane, 5.62 mmol, 3.51 mL) is added drop wise. The mixture is stirred at −78° C. for 45 min then a solution of (1-Formyl-propyl)-carbamic acid tert-butyl ester (2.81 mmol, 0.526 g) in dry THF (3 mL) is added slowly. The mixture is stirred at −78° C. for 4 h, then warmed to 0° C. and quenched by adding 30 mL of 10% (vol) HOAc in ethanol. The mixture is stirred at room temperature for 18 hr and then concentrated in vacuum. The residue is purified over 90 g of silica gel, eluted with ethyl acetate: heptane (1:2 then 1:1) to afford {(S)-1-[hydroxy-(5-thiophen-2-yl-oxazol-2-yl)-methyl]-propyl}-carbamic acid tert-butyl ester (363 mg, 38%) as an oil.

Workup

  1. temperaturecooled to −78° C.
  2. stirringThe mixture is stirred at −78° C. for 45 min
  3. stirringThe mixture is stirred at −78° C. for 4 h
  4. temperaturewarmed to 0° C.
  5. customquenched
  6. additionby adding 30 mL of 10% (vol) HOAc in ethanol
  7. stirringThe mixture is stirred at room temperature for 18 hr
  8. concentrationconcentrated in vacuum
  9. customThe residue is purified over 90 g of silica gel
  10. washeluted with ethyl acetate: heptane (1:2

Sources & evidence

ORD record
ord-d1cd03a1e3a94637896e1b4f7b6a7f0b
Source dataset
uspto-grants-2009_01
Patent number
US07482448B2

Reaction notes

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