Chloroacetyl chloride → HCID 57748794, compound

HRID 1670615Notes

Reaction equation

HRID 1670615 reaction equation
Cl[CH2:2][C:3](Cl)=[O:4].Cl.[Br:7][C:8]1[CH:13]=[CH:12][C:11]([NH:14][C@@H:15]2[CH2:19][NH:18][C@H:17]([CH2:20][OH:21])[CH2:16]2)=[C:10]([N+:22]([O-:24])=[O:23])[CH:9]=1.[OH-].[Na+]>O1CCCC1.O>[Br:7][C:8]1[CH:13]=[CH:12][C:11]([NH:14][C@@H:15]2[CH2:19][N:18]3[C@H:17]([CH2:20][O:21][CH2:2][C:3]3=[O:4])[CH2:16]2)=[C:10]([N+:22]([O-:24])=[O:23])[CH:9]=1

Participants

5

Reactant 3

HCID 6577Chloroacetyl chloride2×HCID 14798Sodium HydroxideHCID 131729089HCID 131729089, compound

Product 1

HCID 57748794HCID 57748794, compoundYield 63.8%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

Add chloroacetyl chloride (0.49 mol, 55.7 g) drop wise to a solution of (2S,4S)-[4-(4-bromo-2-nitro-phenylamino)-pyrrolidin-2-yl]-methanol, hydrochloride (0.22 mol, 79 g) in tetrahydrofuran/water (1:1) mixture (1180 mL) at room temperature. Maintain the reaction pH between 10-12 by continuous addition of 4 M sodium hydroxide solution. After complete addition of chloroacetyl chloride, stir the reaction mixture for 4 h at room temperature. Remove tetrahydrofuran under reduced pressure and extract the aqueous layer with dichloromethane. Dry the organic layer over anhydrous sodium sulfate, filter, and concentrate to obtain the title compound (50 g, 62%) as an orange solid. 1H NMR (400 MHz, CDCl3) δ 1.59-1.67 (m, 1H), 2.58-2.64 (m, 1H), 3.40 (t, 1H), 3.71 (dd, 1H), 3.91-4.01 (m, 2H), 4.09 (d, 1H), 4.20 (dd, 1H), 4.29-4.35 (m, 2H), 6.75 (d, 1H), 7.54 (dd, 1H), 8.05 (d, 1H), 8.32 (d, 1H).

Workup

  1. temperatureMaintain the reaction pH between 10-12
  2. extractionRemove tetrahydrofuran under reduced pressure and extract the aqueous layer with dichloromethane
  3. dry with materialDry the organic layer over anhydrous sodium sulfate
  4. filtrationfilter
  5. concentrationconcentrate

Sources & evidence

ORD record
ord-d2c3b1a155fe454aae1931861f20ed58
Source dataset
uspto-grants-2011_08
Patent number
US07994164B2

Reaction notes

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