Dimethyl Sulfoxide → (S)-4-t-Butoxycarbonylamino-5-(biphenyl-4-yl)-pentenoic acid ethyl ester

HRID 327619Notes

Reaction equation

HRID 327619 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[C:11]([O:15][C:16]([NH:18][C@@H:19]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[CH:25][CH:24]=1)[CH2:20]O)=[O:17])([CH3:14])([CH3:13])[CH3:12].C(N(CC)CC)C.[C:42]([CH:47]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([O:44][CH2:45][CH3:46])=[O:43]>C(Cl)Cl.[Cl-].[Na+].O.O>[CH2:45]([O:44][C:42](=[O:43])[CH:47]=[CH:20][C@@H:19]([NH:18][C:16]([O:15][C:11]([CH3:13])([CH3:12])[CH3:14])=[O:17])[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)=[CH:25][CH:24]=1)[CH3:46]

Participants

9

Reactant 5

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 70670Acetic acid, 2-(triphenylphosphoranylidene)-, ethyl esterHCID 54340554(S)-tert-Butyl (1-([1,1'-biphenyl]-4-yl)-3-hydroxypropan-2-yl)carbamate

Product 1

HCID 54107369(S)-4-t-Butoxycarbonylamino-5-(biphenyl-4-yl)-pentenoic acid ethyl ester

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent4×HCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of oxalyl chloride (0.535 mL, 6.14 mmol) in methylene chloride (3 mL) cooled to -70° under nitrogen is added dropwise dimethylsulfoxide (0.830 mL, 10.7 mmol) in methylene chloride (3 mL). After 20 minutes of stirring at -70°, a solution of (S)-2-t-butoxycarbonylamino-3-(biphenyl-4-yl)-propan-1-ol (1 g, 3.05 mmol) in methylene chloride (3 mL) is added, followed by triethylamine (2 mL, 14.3 mmol). The solution is allowed to warm up to room temperature over a 1 hour period then poured into brine. Methylene chloride (50 mL) and water (80 mL) are added. The organic layer is separated, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The crude aldehyde is dissolved in methylene chloride (15 mL) and treated with (carboethoxymethylene)-triphenylphosphorane (2.1 g, 6.1 mmol). After stirring at room temperature for 18 hours, silica gel (2 g) is added and the solvent is evaporated under vacuum. The product is purified by flash-chromatography on silica gel, eluting with 25% ethyl acetate in hexane. (S)-4-(t-Butoxycarbonylamino)-5-(biphenyl-4-yl)-pentenoic acid ethyl ester is obtained a white solid, m.p. 91°-94°.

Workup

  1. customThe organic layer is separated
  2. dry with materialdried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. dissolutionThe crude aldehyde is dissolved in methylene chloride (15 mL)
  6. stirringAfter stirring at room temperature for 18 hours
  7. additionsilica gel (2 g) is added
  8. customthe solvent is evaporated under vacuum
  9. customThe product is purified by flash-chromatography on silica gel
  10. washeluting with 25% ethyl acetate in hexane

Sources & evidence

ORD record
ord-406539b9ee7f40fe995458c4ace5f87a
Source dataset
uspto-grants-1993_12
Patent number
US05273990

Reaction notes

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