Triethyl phosphonoacetate → (E)-(R)-4-tert-butoxycarbonylamino-6-(4-heptyloxy-phenyl)-4-methyl-hex-2-enoic acid ethyl ester

HRID 12591

Reaction equation

HRID 12591 reaction equation
[CH2:1]([O:3][C:4](=[O:14])[CH2:5]P(OCC)(OCC)=O)[CH3:2].C([Li])CCC.[C:20]([O:24][C:25](=[O:47])[NH:26][C@:27]([CH:45]=O)([CH3:44])[CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([O:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43])=[CH:32][CH:31]=1)([CH3:23])([CH3:22])[CH3:21].C([O-])(O)=O.[Na+]>C1COCC1.CCOC(C)=O>[CH2:1]([O:3][C:4](=[O:14])/[CH:5]=[CH:45]/[C@@:27]([NH:26][C:25]([O:24][C:20]([CH3:21])([CH3:23])[CH3:22])=[O:47])([CH3:44])[CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([O:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43])=[CH:32][CH:31]=1)[CH3:2]

Participants

7

Reactant 4

HCID 13345Triethyl phosphonoacetateHCID 516892Sodium BicarbonateHCID 59339517[(R)-1-Formyl-3-(4-heptyloxy-phenyl)-1-methyl-propyl]-carbamic acid tert-butyl esterHCID 178418339Butyllithium

Product 1

HCID 58897683(E)-(R)-4-tert-butoxycarbonylamino-6-(4-heptyloxy-phenyl)-4-methyl-hex-2-enoic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of (diethoxy-phosphoryl)-acetic acid ethyl ester (429 mg, 1.92 mMol) in dry THF (7 ml) is added n-butyllithium (0.66 ml, 2.5M in hexane, 1.66 mMol) at −78° C. The mixture was stirred at −78° C. for 1 hour. After that time, a solution of [(R)-1-formyl-3-(4-heptyloxy-phenyl)-1-methyl-propyl]-carbamic acid tert-butyl ester (500 mg, 1.28 mMol) in THF (4 ml) is added and stirring is continued at −78° C. for 1.5 hours. The mixture is allowed to warm to RT and then stirred at RT for 2 hours. The reaction mixture is then poured onto a biphasic mixture of AcOEt and NaHCO3 (saturated aqueous solution) and the aqueous phase is extracted twice with AcOEt. The combined organic layers are dried (Na2SO4) and concentrated under reduced pressure. Column chromatography eluting with 4% AcOEt in toluene gives the title compound as a colourless oil.

Workup

  1. stirringstirring
  2. waitis continued at −78° C. for 1.5 hours
  3. temperatureto warm to RT
  4. stirringstirred at RT for 2 hours
  5. extractionthe aqueous phase is extracted twice with AcOEt
  6. dry with materialThe combined organic layers are dried (Na2SO4)
  7. concentrationconcentrated under reduced pressure
  8. washColumn chromatography eluting with 4% AcOEt in toluene

Sources & evidence

ORD record
ord-e219271ff5654914b84b2a1a70a9aa35
Source dataset
uspto-grants-2010_06
Patent number
US07728020B2

Linked notes

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