Propargyl bromide → (4RS,5R,6S)-N-[(tert-butyloxy)carbonyl]-6-amino-5-(triisopropylsilyloxy)-7-cyclohexyl-1-heptyn-4-ol

HRID 375144Notes

Reaction equation

HRID 375144 reaction equation
[Mg].[CH2:2](Br)[C:3]#[CH:4].[C:6]([O:10][C:11]([NH:13][C@@H:14]([CH2:29][CH:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1)[C@@H:15]([O:18][Si:19]([CH:26]([CH3:28])[CH3:27])([CH:23]([CH3:25])[CH3:24])[CH:20]([CH3:22])[CH3:21])[CH:16]=[O:17])=[O:12])([CH3:9])([CH3:8])[CH3:7].[NH4+].[Cl-]>CCOCC.C(Br)C#C.C1(C)C=CC=CC=1.Cl[Hg]Cl>[C:6]([O:10][C:11]([NH:13][C@@H:14]([CH2:29][CH:30]1[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]1)[C@@H:15]([O:18][Si:19]([CH:20]([CH3:21])[CH3:22])([CH:23]([CH3:24])[CH3:25])[CH:26]([CH3:27])[CH3:28])[CH:16]([OH:17])[CH2:4][C:3]#[CH:2])=[O:12])([CH3:7])([CH3:8])[CH3:9]

Participants

9

Reactant 4

HCID 7842Propargyl bromideHCID 25517Ammonium ChlorideHCID 5462224MagnesiumHCID 15281984(2R,3S)-N-[(tert-Butyloxy)carbonyl]-3-amino-4-cyclohexyl-2-(triisopropylsilyloxy)butanal

Product 1

HCID 18652592(4RS,5R,6S)-N-[(tert-butyloxy)carbonyl]-6-amino-5-(triisopropylsilyloxy)-7-cyclohexyl-1-heptyn-4-olYield 66.5%

Reagents, catalysts & solvents 4

HCID 7842Propargyl bromideCatalystHCID 24085Mercuric ChlorideCatalystHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent3×

Conditions

Temperature
10 °C

Procedure

To a solution of magnesium metal (16.4 mmol) and HgCl2 (0.03 g) in Et2O (4 mL) in a flask at room temperature was added several drops of 80% propargyl bromide (16.4 mmol) solution in toluene (1.82 mL) contained in an addition funnel. The mixture turned cloudy. Ether (10 mL) was then added to both the flask and to the propargyl bromide solution in the addition funnel. The funnel solution was added dropwise to the reaction mixture which was cooled to 10° C. The white opaque mixture was stirred for 45 minutes at room temperature after the addition was completed. A solution of the title aldehyde of Step 4 (4.64 mmol) in Et2O (10 mL) was added dropwise to the flask at room temperature. After 2 h at room temperature, the mixture was cooled down to 0° C. and a saturated NH4Cl solution (25 mL) was added. The Et2O layer was collected and the aqueous layer was extracted with Et2O (10 mL). The combined organic layers were washed with water (10 mL), brine (10 mL) and then dried over MgSO4. After evaporation, the residue (a clear, yellow liquid) was purified by medium column chromatography (10% EtOAc in hexane) to give the title alkyne (1.49 g, 66.5% yield). The 1H, 13C and APT NMR spectral data were consistent for the proposed structure.

Workup

  1. customcontained in an addition funnel
  2. additionThe funnel solution was added dropwise to the reaction mixture which
  3. additionafter the addition
  4. waitAfter 2 h at room temperature
  5. temperaturethe mixture was cooled down to 0° C.
  6. customThe Et2O layer was collected
  7. extractionthe aqueous layer was extracted with Et2O (10 mL)
  8. washThe combined organic layers were washed with water (10 mL), brine (10 mL)
  9. dry with materialdried over MgSO4
  10. customAfter evaporation
  11. customthe residue (a clear, yellow liquid) was purified by medium column chromatography (10% EtOAc in hexane)

Sources & evidence

ORD record
ord-70b43b6d252342f9b84e909d701ddf48
Source dataset
uspto-grants-1996_01
Patent number
US05484812

Reaction notes

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