1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → (E)-11,11-difluoro-1-((S)-4-isopropyl-5,5-diphenyl-2-thioxo-oxazolidin-3-yl)-octadec-3-en-1-one

HRID 1779147Notes

Reaction equation

HRID 1779147 reaction equation
[F:1][C:2]([F:22])([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]/[CH2:11][C:12]([OH:14])=O.[CH:23]([C@H:26]1[C:30]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[O:29][C:28](=[S:43])[NH:27]1)([CH3:25])[CH3:24].Cl.C(N=C=NCCCN(C)C)C.P([O-])(O)(O)=O.[Na+]>ClCCl.CN(C1C=CN=CC=1)C.C(OCC)(=O)C>[F:22][C:2]([F:1])([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]/[CH2:11][C:12]([N:27]1[C@@H:26]([CH:23]([CH3:25])[CH3:24])[C:30]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[O:29][C:28]1=[S:43])=[O:14]

Participants

8

Reactant 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 23672064Monosodium phosphateHCID 39058337(S)-4-Isopropyl-5,5-diphenyloxazolidine-2-thioneHCID 90060176(E)-11,11-difluoro-octadec-3-enoic acid

Product 1

HCID 90060316(E)-11,11-difluoro-1-((S)-4-isopropyl-5,5-diphenyl-2-thioxo-oxazolidin-3-yl)-octadec-3-en-1-oneYield 34%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Under a nitrogen atmosphere, (E)-11,11-difluoro-octadec-3-enoic acid (No. 6893453; 502.7 mg, 1.58 mmol) obtained in step B-4 and a commercially available reagent (S)-4-isopropyl-5,5-diphenyl-oxazolidine-2-thione (469.5 mg, 1.58 mmol) were dissolved in dichloromethane (7.5 mL), and the solution was cooled to 0° C. While maintaining the temperature at 0° C., N,N-dimethyl-4-aminopyridine (4-DMAP; 19.3 mg, 0.158 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (WSCl; 393.4 mg, 2.05 mmol) were sequentially added, and the mixture was stirred at 0° C. for 2 minutes and at room temperature for 19 hours. An aqueous solution (9.0 mL) of 10% sodium dihydrogen phosphate and ethyl acetate were added to the reaction solution before extraction. The organic layer was sequentially washed with water and a saturated brine, and dried over anhydrous sodium sulfate. After the organic layer was filtered and the solvent was distilled off, the resulting residue was purified with SP1 (SiO2 cartridge, 10% ethyl acetate/n-hexane, Rf=0.6) to obtain (E)-11,11-difluoro-1-((S)-4-isopropyl-5,5-diphenyl-2-thioxo-oxazolidin-3-yl)-octadec-3-en-1-one (No. 5547308; 647.9 mg, 3 steps, 34% yield).

Workup

  1. custom502.7 mg, 1.58 mmol) obtained in step B-4
  2. temperatureWhile maintaining the temperature at 0° C.
  3. washThe organic layer was sequentially washed with water
  4. dry with materiala saturated brine, and dried over anhydrous sodium sulfate
  5. filtrationAfter the organic layer was filtered
  6. distillationthe solvent was distilled off
  7. customthe resulting residue was purified with SP1 (SiO2 cartridge, 10% ethyl acetate/n-hexane, Rf=0.6)

Sources & evidence

ORD record
ord-5547e5bce77a4df09fdb9469b329638c
Source dataset
uspto-grants-2016_02
Patent number
US09266853B2

Reaction notes

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