Dichloroacetyl chloride → HCID 15887433, compound

HRID 277803Notes

Reaction equation

HRID 277803 reaction equation
[CH3:1][C:2]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:24][C@H:23]([CH2:25][NH2:26])[O:22][C:21]3=[O:27])=[CH:16][C:15]=2[F:28])[CH2:10][CH2:9]1)=[O:7])([CH3:4])[CH3:3].C(N(CC)CC)C.[Cl:36][CH:37]([Cl:41])[C:38](Cl)=[O:39]>C(Cl)Cl>[CH3:4][C:2]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:24][C@H:23]([CH2:25][NH:26][C:38](=[O:39])[CH:37]([Cl:41])[Cl:36])[O:22][C:21]3=[O:27])=[CH:16][C:15]=2[F:28])[CH2:12][CH2:13]1)=[O:7])([CH3:1])[CH3:3]

Participants

5

Reactant 3

HCID 6593Dichloroacetyl chlorideHCID 8471TriethylamineHCID 54424107HCID 54424107, compound

Product 1

HCID 15887433HCID 15887433, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of (S)-(−)-4-[4-[5-(aminomethyl)-2-oxo-3-oxazolidinyl]-2-fluorophenyl]-1-piperidinecarboxylic acid 1,1-dimethylethyl ester (EXAMPLE 20, Step 8, 400 mg) in dry methylene chloride (4.1 mL) at 0° C. under N2 is treated with triethylamine (0.21 mL) and dichloroacetyl chloride (0.11 mL), and the resulting mixture is stirred at 0° C. for three hours, diluted with methylene chloride (10 mL), washed with water (10 mL), saturated aqueous sodium bicarbonate (10 mL) and saline (10 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product which is then chromatographed on silica gel (70-230 mesh, 50 g), eluting with methanol/chloroform (5/95). Pooling and concentration of those fractions with an Rf=0.53 by TLC (methanol/chloroform, 10/90), trituration with methylene chloride/diethyl ether and filtration gives the title compound, mp 168-170° C.

Workup

  1. washwashed with water (10 mL), saturated aqueous sodium bicarbonate (10 mL) and saline (10 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customto give the crude product which
  5. customis then chromatographed on silica gel (70-230 mesh, 50 g)
  6. washeluting with methanol/chloroform (5/95)
  7. filtrationPooling and concentration of those fractions with an Rf=0.53 by TLC (methanol/chloroform, 10/90), trituration with methylene chloride/diethyl ether and filtration

Sources & evidence

ORD record
ord-8dfca3348e454b2e8b964fca39174053
Source dataset
uspto-grants-2002_03
Patent number
US06358942B1

Reaction notes

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