1,2-Dichloroethane → HCID 25142331, compound

HRID 1920761Notes

Reaction equation

HRID 1920761 reaction equation
[C:1]([N:5]1[CH2:10][CH2:9][CH:8]([CH2:11][C:12]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=O)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].CC1C=CC=C(C)N=1.ClCCCl.[Cl:33][C:34]1[CH:42]=[CH:41][CH:40]=[C:39]([CH2:43][C:44](=[O:57])[NH:45][C@@H:46]([CH:54]2[CH2:56][CH2:55]2)[C:47]2[CH:52]=[CH:51][CH:50]=[C:49]([F:53])[CH:48]=2)[C:35]=1[C:36](O)=[O:37]>>[CH:54]1([C@H:46]([NH:45][C:44]([C:43]2[C:39]3[C:35](=[C:34]([Cl:33])[CH:42]=[CH:41][CH:40]=3)[C:36](=[O:37])[N:14]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:12]=2[CH2:11][CH:8]2[CH2:7][CH2:6][N:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:10][CH2:9]2)=[O:57])[C:47]2[CH:52]=[CH:51][CH:50]=[C:49]([F:53])[CH:48]=2)[CH2:56][CH2:55]1

Participants

5

Reactant 4

HCID 111,2-DichloroethaneHCID 79372,6-LutidineHCID 57733287HCID 57733287, compoundHCID 57733292HCID 57733292, compound

Product 1

HCID 25142331HCID 25142331, compoundYield 15.8%

Conditions

Temperature
0 °C

Procedure

To a cold (ice bath) mixture of 2-(1-tert-butyl-piperidin-4-yl)-N-phenyl-acetamide (250 mg, 0.91 mmol) and 2,6-dimethylpyridine (0.139 ml, 1.2 mmol) in 1,2-dichloroethane (8 ml) oxalyl chloride (0.07 ml, 0.8 mmol) was added and stirred at 0° C. for 15 min. 2-Chloro-6-({[(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-carbamoyl}-methyl)-benzoic acid (70 mg, 0.2 mmol) was added and the reaction mixture was stirred in a sealed vessel at 90° C. for 15 hours. It was partitioned between 0.5 M aq. NaOH (40 ml) and ethyl acetate (200 ml), the organic phase washed with water, dried and evaporated. The residue was purified by flash chromatography (SiO2, ethyl acetate-methanol) to give 19 mg of the title compound. LC-MS (m/z) 600.6 (MH+); tR=1.1. 1H NMR (500 MHz, r.t., DMSO-d6): broad signals, a mixture of two atropisomers.

Workup

  1. additionwas added
  2. stirringthe reaction mixture was stirred in a sealed vessel at 90° C. for 15 hours
  3. customIt was partitioned between 0.5 M aq. NaOH (40 ml) and ethyl acetate (200 ml)
  4. washthe organic phase washed with water
  5. customdried
  6. customevaporated
  7. customThe residue was purified by flash chromatography (SiO2, ethyl acetate-methanol)

Sources & evidence

ORD record
ord-6bdac7576fb241b4b11f97ff812ea465
Source dataset
uspto-grants-2012_05
Patent number
US08173639B2

Reaction notes

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