Chloroform → HCID 19040993, compound

HRID 2399954Notes

Reaction equation

HRID 2399954 reaction equation
[C:1]([C:3]1[CH:31]=[CH:30][C:6]([O:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]2[CH:28]=[CH:27][C:17]([C:18]([N:20]([CH:24]([CH3:26])[CH3:25])[CH:21]([CH3:23])[CH3:22])=[O:19])=[C:16]([OH:29])[CH:15]=2)=[CH:5][CH:4]=1)#[N:2].[OH-:32].[Na+].C(Cl)(Cl)Cl>CC(C)=O>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([O:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]2[CH:28]=[CH:27][C:17]([C:18](=[O:19])[N:20]([CH:24]([CH3:25])[CH3:26])[CH:21]([CH3:23])[CH3:22])=[C:16]([CH:15]=2)[O:29][C:17]([CH3:27])([CH3:16])[C:18]([OH:19])=[O:32])=[CH:30][CH:31]=1)#[N:2]

Participants

5

Reactant 3

HCID 6212ChloroformHCID 14798Sodium HydroxideHCID 19040962HCID 19040962, compound

Product 1

HCID 19040993HCID 19040993, compound

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent2×

Procedure

A stirred, refluxing mixture of 4-[5-(4-cyanophenoxy)pentyloxy]-2-hydroxy-N,N-bis(1-methylethyl)benzamide (0.5 g, 1.18 mmol), sodium hydroxide (480 mg, 1.2 mmol), and 50 mL of acetone is treated with chloroform (125 uL, 1.6 mmol) in 20 mL of acetone. The reaction is refluxed for 4 hours and concentrated in vacuo. The resulting material is partitioned between ethyl acetate and 1N hydrochloric acid. The organic layer is washed with brine, dried over magnesium sulfate and concentrated. The resulting material is purified by chromatography on silica gel (20 g) with 40-100% ethyl acetate/hexane followed by 10% MeOH/ethyl acetate as the eluent to afford 5-[5-[4-cyanophenoxy]pentyloxy]-2-[N,N-bis(1-methylethyl)carbamoyl]phenoxydimethylacetic acid as colorless foam. A stirred, 0° C. solution of 5-[5-[4-cyanophenoxylpentyloxy]-2-[N,N-bis(1-methylethyl)carbamoyl]phenoxydimethylacetic acid (210 mg, 0.411 mmol) in 2.0 mL of anhydrous dichloromethane and 150 mL of anhydrous ethanol at 0° C. is treated with anhydrous hydrogen chloride gas over 30 minutes. This solution is stirred at room temperature for 20 hours and the resulting solution is concentrated in vacuo. The resulting ethyl 4-[5-[3-ethoxycarbonyldimethylmethoxy-4-[N,N-bis(1-methylethyl)aminocarbonyl]phenoxylpentyloxylbenzenecarboximidoate monohydrochloride is then dissolved in 50 mL of anhydrous ethanol in a pressure tube, and treated with anhydrous ammonia for 5 minutes at 0° C. The pressure tube is sealed and heated to 100° C. for 1 hour. Upon cooling and concentrating in vacuo, the resulting material is purified by chromatography on silica gel (15 g) with 5-20% methanol/dichloromethane as the eluent to afford ethyl 5-[5-[4-(aminoiminomethyl)phenoxy]pentyloxyl-2-[N,N-bis(1-methylethyl)carbamoyl]phenoxydimethylacetate monohydrochloride as colorless foam.

Workup

  1. temperatureA stirred, refluxing
  2. temperatureThe reaction is refluxed for 4 hours
  3. concentrationconcentrated in vacuo
  4. customThe resulting material is partitioned between ethyl acetate and 1N hydrochloric acid
  5. washThe organic layer is washed with brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. customThe resulting material is purified by chromatography on silica gel (20 g) with 40-100% ethyl acetate/hexane

Sources & evidence

ORD record
ord-bc39d604ec9046148a5231ccf1b13f09
Source dataset
uspto-grants-1995_09
Patent number
US05451700

Reaction notes

Loading…