Hydrochloric Acid → HCID 68000688, compound

HRID 1048601Notes

Reaction equation

HRID 1048601 reaction equation
[C:1](Cl)(=[O:5])[C:2](Cl)=[O:3].[Cl:7][C:8]1[CH:9]=[C:10]([C@@H:14]2[C@@H:19]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)[N:18]([C@@H:27]([CH:34]3[CH2:36][CH2:35]3)[CH2:28][S:29]([CH2:32][CH3:33])(=[O:31])=[O:30])[C:17](=[O:37])[C@:16]([CH2:39]C(O)=O)([CH3:38])[CH2:15]2)[CH:11]=[CH:12][CH:13]=1.C[Si](C)(C)OC=C(O[Si](C)(C)C)O[Si](C)(C)C.Cl>ClCCl.O.C1COCC1>[Cl:7][C:8]1[CH:9]=[C:10]([C@@H:14]2[C@@H:19]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)[N:18]([C@@H:27]([CH:34]3[CH2:36][CH2:35]3)[CH2:28][S:29]([CH2:32][CH3:33])(=[O:30])=[O:31])[C:17](=[O:37])[C@:16]([CH2:38][C:1](=[O:5])[CH2:2][OH:3])([CH3:39])[CH2:15]2)[CH:11]=[CH:12][CH:13]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 65578Oxalyl chlorideHCID 553067(Vinyl-2-ylidenetris(oxy))tris(trimethylsilane)HCID 58573631HCID 58573631, compound

Product 1

HCID 68000688HCID 68000688, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Oxalyl chloride (0.063 ml, 0.715 mmol) was added to a solution of 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-cyclopropyl-2-(ethylsulfonyl)ethyl)-3-methyl-2-oxopiperidin-3-yl)acetic acid (Example 349, 0.316 g, 0.572 mmol) in dichloromethane (1.9 ml). The reaction was stirred for 3 h at room temperature. The solvents were removed in vacuo. To the solids was added tris(trimethylsiloxy)ethylene (0.42 ml, 1.26 mmol) and the reaction was stirred at 90° C. After 2 h, the reaction was cooled, charged with THF (1 mL) and HCl (1.4 M, 0.982 ml, 1.375 mmol), and brought to reflux for 30 min. After cooling, the reaction was poured into water (20 mL) and extracted with dichloromethane (3×20 mL). The combined organics were dried over sodium sulfate and concentrated in vacuo. Silica gel chromatography (step gradient elution 1 to 5% 2 M ammonia in MeOH in dichloromethane) afforded the title compound.

Workup

  1. customThe solvents were removed in vacuo
  2. stirringthe reaction was stirred at 90° C
  3. waitAfter 2 h
  4. temperaturethe reaction was cooled
  5. temperatureto reflux for 30 min
  6. temperatureAfter cooling
  7. extractionextracted with dichloromethane (3×20 mL)
  8. dry with materialThe combined organics were dried over sodium sulfate
  9. concentrationconcentrated in vacuo
  10. washSilica gel chromatography (step gradient elution 1 to 5% 2 M ammonia in MeOH in dichloromethane)

Sources & evidence

ORD record
ord-9204dc70e99e4fa698bb08699a461110
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

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