Pivaloyl chloride → N-{3-[4-(chloroacetyl)phenyl]propionyl} alanine methyl ester

HRID 2419372Notes

Reaction equation

HRID 2419372 reaction equation
C(Cl)(=O)C(C)(C)C.[Cl:8][CH2:9][C:10]([C:12]1[CH:17]=[CH:16][C:15]([CH2:18][CH2:19][C:20]([OH:22])=O)=[CH:14][CH:13]=1)=[O:11].Cl.[CH3:24][O:25][C:26](=[O:30])[CH:27]([CH3:29])[NH2:28].C(=O)(O)[O-].[Na+]>O1CCCC1.C(#N)C.CN(C)C=O.C(N(CC)CC)C>[CH3:24][O:25][C:26](=[O:30])[C@H:27]([CH3:29])[NH:28][C:20](=[O:22])[CH2:19][CH2:18][C:15]1[CH:14]=[CH:13][C:12]([C:10](=[O:11])[CH2:9][Cl:8])=[CH:17][CH:16]=1

Participants

9

Reactant 4

HCID 62493Pivaloyl chlorideHCID 516892Sodium BicarbonateHCID 2756298Alanine, methyl ester, hydrochloride (1:1)HCID 203155713-[4-(Chloroacetyl)phenyl]propionic acid

Product 1

HCID 53760308N-{3-[4-(chloroacetyl)phenyl]propionyl} alanine methyl ester

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent2×

Conditions

Temperature
-15 °C

Procedure

A solution of pivaloyl chloride (4.41ml.) in tetrahydrofuran (30ml.) was added to a stirred solution, cooled to -15° C., of 3-[4-(chloroacetyl)phenyl]propionic acid (9.7g.) and triethylamine (5.5ml.) in tetrahydrofuran (30ml.) and acetonitrile (40ml.). The resultant mixture was stirred for one hour at -15° C. A suspension of DL-alanine methyl ester hydrochloride (5.0g.) in dimethylformamide (30ml.) containing triethylamine (5.5ml.) was then added over 15 minutes. The mixture was stirred at -15° C. for 1 hour and then for 16 hours at room temperature. Saturated sodium bicarbonate solution (30ml.) was added and the solution was stirred for 30 minutes and then evaporated in vacuo. The residue was mixed with water (150ml.) and was extracted with chloroform (2 × 100ml.). The extracts were washed successively with 10% hydrochloric acid (200ml.), water (200ml.), saturated sodium bicarbonate solution (200ml.) and water (200ml.), dried (MgSO 4) and evaporated. The residue was recrystallised from toluene/petrol to give N-{3-[4-(chloroacetyl)phenyl]propionyl} alanine methyl ester, m.p. 122°-124° C.

Workup

  1. additionwas then added over 15 minutes
  2. waitfor 16 hours at room temperature
  3. stirringthe solution was stirred for 30 minutes
  4. customevaporated in vacuo
  5. additionThe residue was mixed with water (150ml.)
  6. extractionwas extracted with chloroform (2 × 100ml.)
  7. washThe extracts were washed successively with 10% hydrochloric acid (200ml.), water (200ml.), saturated sodium bicarbonate solution (200ml.) and water (200ml.)
  8. dry with materialdried (MgSO 4)
  9. customevaporated
  10. customThe residue was recrystallised from toluene/petrol

Sources & evidence

ORD record
ord-9a71e656c3604e6fbaef698fa778409f
Source dataset
uspto-grants-1978_08
Patent number
US04105790

Reaction notes

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