Ammonium Chloride → (R)-3-((S)-4-(2,4-difluoro phenyl)-2-(hydroxymethyl)pent-4-enoyl)-4-phenyloxazolidin-2-one

HRID 512803Notes

Reaction equation

HRID 512803 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9](=[CH2:26])[CH2:10][CH2:11][C:12]([N:14]1[C@H:18]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:17][O:16][C:15]1=[O:25])=[O:13].C(N(C(C)C)CC)(C)C.[O:36]1[CH2:41]CCOO1.[Cl-].[NH4+]>ClCCl.[Cl-].[Ti+4].[Cl-].[Cl-].[Cl-]>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9](=[CH2:26])[CH2:10][C@@H:11]([CH2:41][OH:36])[C:12]([N:14]1[C@H:18]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:17][O:16][C:15]1=[O:25])=[O:13]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 19593658CID 19593658HCID 71534790(R)-3-(4-(2,4-difluorophenyl)pent-4-enoyl)-4-phenyl oxazolidin-2-one

Product 1

HCID 89463443(R)-3-((S)-4-(2,4-difluoro phenyl)-2-(hydroxymethyl)pent-4-enoyl)-4-phenyloxazolidin-2-one

Reagents, catalysts & solvents 2

HCID 160960Diamminetetrachlorotitanate(IV)Catalyst2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
-15 °C

Procedure

Titanium chloride solution (prepared from 33.8 ml of titanium chloride and 50 ml of dichloromethane) was added to a pre-cooled solution of (R)-3-(4-(2,4-difluorophenyl)pent-4-enoyl)-4-phenyloxazolidin-2-one compound of formula-4 (100 g) in dichloro methane (1000 ml) at −20 to −10° C. under nitrogen atmosphere and diisopropyl ethylamine (45.61 μm) was added to the reaction mixture and stirred for 40 minutes at −20 to −10° C. A trioxane solution (prepared from 52.94 g of trioxane and 150 ml of dichloro methane) was added to the reaction mixture at −20 to −10° C. and followed by titanium chloride solution (prepared from 33.8 ml of titanium chloride and 50 ml of dichloro methane) at −20 to −10° C. Temperature of the reaction mixture was raised to −5 to 0° C. and stirred for 2 hours at −5 to 0° C. After completion of the reaction, the reaction mixture was added to 10% ammonium chloride at 10-15° C. Both organic and aqueous layers were separated and the aqueous layer was extracted with dichloro methane. Both the dichloro methane layers were combined and washed with water followed by 10% sodium chloride solution. The obtained dichloro methane layer was taken to the next step without isolating the title compound.

Workup

  1. temperatureTemperature of the reaction mixture was raised to −5 to 0° C.
  2. stirringstirred for 2 hours at −5 to 0° C
  3. customAfter completion of the reaction
  4. customBoth organic and aqueous layers were separated
  5. extractionthe aqueous layer was extracted with dichloro methane
  6. washwashed with water

Sources & evidence

ORD record
ord-88784880456a41eeb36ea4151e0441c5
Source dataset
uspto-grants-2015_08
Patent number
US09102664B2

Reaction notes

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