Citric Acid → HCID 90060123, compound

HRID 1779173Notes

Reaction equation

HRID 1779173 reaction equation
[CH2:1]([O:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][C@H:13]([NH:18][C:19]([C@@H:21](/[CH:30]=[CH:31]/[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][C:38]([F:47])([F:46])[CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH3:45])[C@@:22]([OH:29])([CH2:26][CH2:27][CH3:28])[C:23]([OH:25])=[O:24])=[O:20])[C:14]([O:16]C)=[O:15])=[CH:8][CH:7]=1)[C:2]#[C:3][CH3:4].C(N(CC)CC)C.[Br-].[Li+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(#N)C.O.C(OCC)(=O)C>[CH2:1]([O:5][C:6]1[CH:7]=[CH:8][C:9]([CH2:12][C@H:13]([NH:18][C:19]([C@@H:21](/[CH:30]=[CH:31]/[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][C:38]([F:46])([F:47])[CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH3:45])[C@@:22]([OH:29])([CH2:26][CH2:27][CH3:28])[C:23]([OH:25])=[O:24])=[O:20])[C:14]([OH:16])=[O:15])=[CH:10][CH:11]=1)[C:2]#[C:3][CH3:4]

Participants

8

Reactant 4

HCID 311Citric AcidHCID 8471TriethylamineHCID 82050Lithium BromideHCID 118157567HCID 118157567, compound

Product 1

HCID 90060123HCID 90060123, compoundYield 84%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

At room temperature, (E)-(2S,3S)-3-[(S)-2-(4-but-2-ynyloxy-phenyl)-1-methoxycarbonyl-ethylcarbamoyl]-12,12-difluoro-2-hydroxy-2-propyl-nonadec-4-enoic acid (No. 5501824; 27.5 mg, 0.041 mmol) was dissolved in acetonitrile (0.55 mL) and water (22 μL), and triethylamine (34.6 μL, 0.249 mmol) and lithium bromide (72.0 mg, 0.829 mmol) were added in order. The mixture was stirred at 50° C. for 2.0 hours, and cooled to room temperature. The progress of the reaction was then stopped by adding an aqueous solution of 0.5 M citric acid. Ethyl acetate was added, and the mixture was extracted. The organic layer was washed with water, dried over anhydrous sodium sulfate, and filtered. The solvent was distilled off. The residue was then purified by preparative HPLC (water with 0.05% TFA-acetonitrile with 0.05% TFA) to obtain (E)-(2S,3S)-3-[(S)-2-(4-but-2-ynyloxy-phenyl)-1-carboxy-ethylcarbamoyl]-12,12-difluoro-2-hydroxy-2-propyl-nonadec-4-enoic acid (No. 5501825; 22.4 mg, 84% yield, white powder).

Workup

  1. customAt room temperature
  2. temperaturecooled to room temperature
  3. extractionthe mixture was extracted
  4. washThe organic layer was washed with water
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. distillationThe solvent was distilled off
  8. customThe residue was then purified by preparative HPLC (water with 0.05% TFA-acetonitrile with 0.05% TFA)

Sources & evidence

ORD record
ord-9c8b241ebb1b4903a6721a205bfa2680
Source dataset
uspto-grants-2016_02
Patent number
US09266853B2

Reaction notes

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