Acetic Acid → (R)-5-(2-(3,5-difluorophenylamino)ethyl)-2,2-dimethyl-1,3-dioxolan-4-one

HRID 1098682Notes

Reaction equation

HRID 1098682 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([F:9])[CH:8]=1)[NH2:5].[CH3:10][C:11]1([CH3:20])[O:15][C@H:14]([CH2:16][CH:17]=O)[C:13](=[O:19])[O:12]1.C(O)(=O)C.[BH4-].[Na+]>ClCCCl>[F:1][C:2]1[CH:3]=[C:4]([NH:5][CH2:17][CH2:16][C@H:14]2[O:15][C:11]([CH3:20])([CH3:10])[O:12][C:13]2=[O:19])[CH:6]=[C:7]([F:9])[CH:8]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 965953,5-DifluoroanilineHCID 4311764Sodium borohydrideHCID 24864236HCID 24864236, compound

Product 1

HCID 59140613(R)-5-(2-(3,5-difluorophenylamino)ethyl)-2,2-dimethyl-1,3-dioxolan-4-oneYield 96%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a stirred solution of 3,5-difluoroaniline (4.0 g, 31.0 mmol), (R)-2-(2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl)acetaldehyde (4.9 g, 31.0 mmol) and acetic acid (1.7 ml, 31.0 mmol) in 1,2-dichloroethane (100 mL) under nitrogen at 0° C. was added sodium borohydride (1.17 g, 31.0 mmol mol) in portions over 10 minutes. The resulting mixture was stirred at RT for 2.5 hours. After cooling to 0° C. the reaction mixture was quenched by the careful addition of saturated aqueous NaHCO3 (100 mL) followed by DCM (100 mL). The phases were separated and the aqueous phase was extracted with dichloromethane (2×100 mL). The combined organic extracts were dried over MgSO4 and concentrated under reduced pressure to provide the crude (R)-5-[2-(3,5-difluorophenylamino)ethyl]-2,2-dimethyl-1,3-dioxolan-4-one as a yellow oil (8.07 g, 29.7 mmol, 96% yield) which was used without any further purification in the next reaction step. LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA), m/z: M+1 obs=272.3; tR=1.76 min.

Workup

  1. temperatureAfter cooling to 0° C. the reaction mixture
  2. customwas quenched by the careful addition of saturated aqueous NaHCO3 (100 mL)
  3. customThe phases were separated
  4. extractionthe aqueous phase was extracted with dichloromethane (2×100 mL)
  5. dry with materialThe combined organic extracts were dried over MgSO4
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-37c48065cc414a4ba2ad47e5bf10ea9a
Source dataset
uspto-grants-2012_03
Patent number
US08143297B2

Reaction notes

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