Hydrochloric Acid → 2-[3-(4-Chlorophenyl)-1,2-benzoxazol-7-yl]propanoic acid

HRID 1606023Notes

Reaction equation

HRID 1606023 reaction equation
[CH2:1]([Li])CCC.C(NC(C)C)(C)C.[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[C:24]3[CH:25]=[CH:26][CH:27]=[C:28]([CH2:29][C:30]([OH:32])=[O:31])[C:23]=3[O:22][N:21]=2)=[CH:16][CH:15]=1.CI.Cl>O1CCCC1.CN(C)P(N(C)C)(N(C)C)=O>[CH3:1][CH:29]([C:28]1[C:23]2[O:22][N:21]=[C:20]([C:17]3[CH:16]=[CH:15][C:14]([Cl:13])=[CH:19][CH:18]=3)[C:24]=2[CH:25]=[CH:26][CH:27]=1)[C:30]([OH:32])=[O:31]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 7912DiisopropylamineHCID 30439721,2-Benzisoxazole-7-acetic acid, 3-(p-chlorophenyl)-HCID 178418339Butyllithium

Product 1

HCID 30439732-[3-(4-Chlorophenyl)-1,2-benzoxazol-7-yl]propanoic acid

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 12679HexamethylphosphoramideSolvent

Conditions

Temperature
5 °C

Procedure

n-Butyl lithium (31ml, 46m Mole of 1.5M) was cooled to -30°C under nitrogen with stirring and treated with a solution of diisopropylamine (6.25 ml. 4.65g., 46m Mole) in tetrahydrofuran (38ml) keeping the temperature at -30° to -50°C. A solution of the acetic acid of Example 35 (4.5g, 15.64m Mole) in THF (38ml) and hexamethylphosphoramide (38ml) was added dropwise to the Bu Li solution and the solution stirred at -30° to -40°C for 1.5 hours. It was then transferred to a solution of methyliodide (150ml) which was stirred and had been cooled to 5° C. in an ice bath. The mixture was stirred in the melting ice bath for 1.5 hours, acidified with a little conc. HCl, evaporated to small bulk and treated with water (500ml). The mixture was extracted with chloroform which was dried (Na2SO4) and evaporated to leave the α-methyl acetic acid as a mixture with its methyl ester. This was refluxed with conc. HCl (60ml) and acetic acid (30ml) for four hours, diluted with water, extracted with chloroform, which was dried (Na2SO4), evaporated to leave a gum which was purified on preparative thin layer chromotography to give the α-methyl acetic acid (0.85g), m.p. 136°-138°C.

Workup

  1. customat -30° to -50°C
  2. stirringthe solution stirred at -30° to -40°C for 1.5 hours
  3. stirringwas stirred
  4. customevaporated to small bulk
  5. additiontreated with water (500ml)
  6. extractionThe mixture was extracted with chloroform which
  7. dry with materialwas dried (Na2SO4)
  8. customevaporated

Sources & evidence

ORD record
ord-77b3db64889b415fbe864c930077e0ed
Source dataset
uspto-grants-1976_04
Patent number
US03951999

Reaction notes

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