Dichloromethane → HCID 58234727, compound

HRID 68251Notes

Reaction equation

HRID 68251 reaction equation
[C:1]([O:4][CH2:5][C@@H:6]1[CH2:10][CH2:9][CH2:8][N:7]1[C:11](Cl)=[O:12])(=[O:3])[CH3:2].[F:14][C:15]1[CH:22]=[C:21]([OH:23])[CH:20]=[C:19]([F:24])[C:16]=1[CH:17]=[O:18].C(N(CC)CC)C.C(Cl)Cl>O>[C:1]([O:4][CH2:5][C@@H:6]1[CH2:10][CH2:9][CH2:8][N:7]1[C:11]([O:23][C:21]1[CH:22]=[C:15]([F:14])[C:16]([CH:17]=[O:18])=[C:19]([F:24])[CH:20]=1)=[O:12])(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 249035482,6-Difluoro-4-hydroxybenzaldehydeHCID 582347151296132-58-5

Product 1

HCID 58234727HCID 58234727, compoundYield 50.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a 250 mL dry round bottom flask were added (S)-(1-(chlorocarbonyl)pyrrolidin-2-yl)methyl acetate (6.79 g, 33.0 mmol), 2,6-difluoro-4-hydroxybenzaldehyde (4.74 g, 30 mmol), triethylamine (5.40 mL, 39.0 mmol) and anhydrous CH2Cl2 (40 mL). The resulting mixture was stirred at room temperature for 2 days, then water (80 mL) was added to the reaction mixture. The CH2Cl2 layer was separated, and the aqueous layer was extracted continually with CH2Cl2 (80 mL×2). The combined CH2Cl2 solution was dried over Na2SO4. After removal of the solvent, the residue was purified with a silica gel chromatography (heptane/ethyl acetate, gradient eluting) to give (S)-3,5-difluoro-4-formylphenyl 2-(acetoxymethyl)pyrrolidine-1-carboxylate (4.92 g) as a colorless oil. Yield: 46%. 1H NMR (CDCl3, 300 MHz, mixture of two isomers): δ=10.28 (s, 1H), 6.97 (t, J=11.4 Hz, 2H), 4.33-4.12 (m, 3H), 3.65-3.55 (m, 2H), 2.10-2.01 (m, 7H). 13C NMR (CDCl3, 75.5 MHz, mixture of two isomers): δ=183.5, 170.7 (d, J=7.3 Hz), 163.6 (dd, J=262.5, 8.6 Hz), 157.0, 150.8 (d, J=14.6 Hz), 112.6, 106.2 (d, J=25.0 Hz), 64.4, 63.8, 56.8, 56.4, 47.4, 47.3, 28.7, 27.8, 23.8, 22.9, 20.8.

Workup

  1. customTo a 250 mL dry round bottom flask
  2. customThe CH2Cl2 layer was separated
  3. extractionthe aqueous layer was extracted continually with CH2Cl2 (80 mL×2)
  4. dry with materialThe combined CH2Cl2 solution was dried over Na2SO4
  5. customAfter removal of the solvent
  6. customthe residue was purified with a silica gel chromatography (heptane/ethyl acetate, gradient eluting)

Sources & evidence

ORD record
ord-43f83549f14448e6a1e125294748a519
Source dataset
uspto-grants-2014_09
Patent number
US08822435B2

Reaction notes

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