Water → 3-[4-{2-(4-[Tert-butoxycarbonylamino]phenyl)ethoxy}phenyl]-2-ethoxy-2-methyl-propanoic acid

HRID 987288Notes

Reaction equation

HRID 987288 reaction equation
[OH-].[Na+].[C:3]([O:7][C:8]([NH:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][CH2:18][O:19]S(C2C=CC(C)=CC=2)(=O)=O)=[CH:13][CH:12]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4].C([O:32][C:33](=[O:47])[C:34]([O:44][CH2:45][CH3:46])([CH3:43])[CH2:35][C:36]1[CH:41]=[CH:40][C:39](O)=[CH:38][CH:37]=1)C.O>CS(C)=O.O1CCCC1>[C:3]([O:7][C:8]([NH:10][C:11]1[CH:12]=[CH:13][C:14]([CH2:17][CH2:18][O:19][C:39]2[CH:38]=[CH:37][C:36]([CH2:35][C:34]([O:44][CH2:45][CH3:46])([CH3:43])[C:33]([OH:47])=[O:32])=[CH:41][CH:40]=2)=[CH:15][CH:16]=1)=[O:9])([CH3:4])([CH3:5])[CH3:6]

Participants

7

Reactant 4

HCID 962WaterHCID 14798Sodium Hydroxide2×HCID 113267772-(4-(Tert-butoxycarbonylamino)phenyl]ethyl-4-methylbenzenesulfonateHCID 538891572-Ethoxy-3-(4-hydroxyphenyl)2-methyl propanoic acid ethyl ester

Product 1

HCID 229886853-[4-{2-(4-[Tert-butoxycarbonylamino]phenyl)ethoxy}phenyl]-2-ethoxy-2-methyl-propanoic acidYield 17.6%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydroxide (0.105 g; 2.63 mmole) was pulverized and dissolved in DMSO (8 ml). To 4 ml of this solution 2-[4-(tert-butoxycarbonylamino)phenyl]ethyl-4-methylbenzenesulfonate (described in Example 40a) (0.515 g; 1.316 mmole) and 2-ethoxy-3-(4-hydroxyphenyl)2-methyl propanoic acid ethyl ester (0.331 g; 1.316 mmole) were added and the mixture was stirred at room temperature over night. The remaining volume (4 ml) of the sodium hydroxide solution and water (1 ml) were added. A precipitate was formed which was dissolved by addition of tetrahydrofuran (1 ml). The mixture was allowed to stand over night and was then evaporated. The residue was redissolved in dichloromethane and water and the phases were separated. The water phase was extracted once more with dichloromethane, acidified with hydrochloric acid (1 M), extracted several times with ethyl acetate and diethyl ether. The organic phases were combined, dried with magnesium sulfate and evaporated. Purification of the crude product by flash chromatography and preparative HPLC gave 0.103 g (17.1% yield) of 3-[4-{2-(4[-tert-butoxycarbonylamino]phenyl)ethoxy}phenyl]-2-ethoxy-2-methyl-propanoic acid.

Workup

  1. customA precipitate was formed which
  2. waitto stand over night
  3. customwas then evaporated
  4. dissolutionThe residue was redissolved in dichloromethane
  5. customwater and the phases were separated
  6. extractionThe water phase was extracted once more with dichloromethane
  7. extractionextracted several times with ethyl acetate and diethyl ether
  8. dry with materialdried with magnesium sulfate
  9. customevaporated
  10. customPurification of the crude product by flash chromatography and preparative HPLC

Sources & evidence

ORD record
ord-fa591d7bfbc847e183870e53cd8819b6
Source dataset
uspto-grants-2003_10
Patent number
US06630600B1

Reaction notes

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