Water → trans-7-Chloro-5-(2-chlorophenyl)-1-isobutyl-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetic acid pivaloyloxymethyl ester

HRID 1419029Notes

Reaction equation

HRID 1419029 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH2:12][CH:13]([CH3:15])[CH3:14])[C:10](=[O:16])[C@@H:9]([CH2:17][C:18]([OH:20])=[O:19])[O:8][C@H:7]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[Cl:27])[C:6]=2[CH:28]=1.[C:29]([O:35][CH2:36]Cl)(=[O:34])[C:30]([CH3:33])([CH3:32])[CH3:31].C(N(CC)CC(C)C)C(C)C.O>CN(C)C=O.C(OCC)(=O)C>[C:29]([O:35][CH2:36][O:19][C:18](=[O:20])[CH2:17][C@H:9]1[O:8][C@H:7]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[Cl:27])[C:6]2[CH:28]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=2[N:11]([CH2:12][CH:13]([CH3:14])[CH3:15])[C:10]1=[O:16])(=[O:34])[C:30]([CH3:33])([CH3:32])[CH3:31]

Participants

7

Reactant 4

HCID 962WaterHCID 87885Chloromethyl pivalateHCID 12446309N-Ethyl-2-methyl-N-(2-methylpropyl)propan-1-amineHCID 22883210trans-7-Chloro-5-(2-chlorophenyl)-1-isobutyl-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetic acid

Product 1

HCID 67603055trans-7-Chloro-5-(2-chlorophenyl)-1-isobutyl-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetic acid pivaloyloxymethyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

In N,N-dimethylformamide (10 ml) was dissolved trans-7-chloro-5-(2-chlorophenyl)-1-isobutyl-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetic acid (0.5 g) obtained in Example 2. To the solution were added pivaloyloxymethyl chloride (0.43 ml), N,N-diisobutyl ethylamine (0.52 ml) and KI (0.2 g). The mixture was stirred at room temperature overnight. To the reaction mixture were added water (100 ml) and ethyl acetate (100 ml), followed by extraction. The ethyl acetate layer was washed with an aqueous solution of potassium hydrogensulfate, an aqueous solution of sodium hydrogencarbonate and water, successively, which was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure. The residue was purified by means of a silica gel column chromatography (hexane:ethyl acetate=10:1 to 5:1) to afford trans-7-chloro-5-(2-chlorophenyl)-1-isobutyl-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetic acid pivaloyloxymethyl ester (0.55 g).

Workup

  1. extractionfollowed by extraction
  2. washThe ethyl acetate layer was washed with an aqueous solution of potassium hydrogensulfate
  3. dry with materialan aqueous solution of sodium hydrogencarbonate and water, successively, which was dried over anhydrous magnesium sulfate
  4. distillationThe solvent was then distilled off under reduced pressure
  5. customThe residue was purified by means of a silica gel column chromatography (hexane:ethyl acetate=10:1 to 5:1)

Sources & evidence

ORD record
ord-5b70a28074a84a6c99f1958fac799974
Source dataset
uspto-grants-1999_03
Patent number
US05885979

Reaction notes

Loading…