Hydrochloric Acid → HCID 131729810, compound

HRID 1511846Notes

Reaction equation

HRID 1511846 reaction equation
[CH3:1][O:2][C:3]([C@@:5]1([NH2:17])[CH2:9][CH2:8][C@H:7]([C:10]2[CH:15]=[CH:14][C:13](Br)=[CH:12][CH:11]=2)[CH2:6]1)=[O:4].Cl.[CH:19]#[C:20][CH2:21]CCCCC.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N1CCCCC1.C1COCC1.[C:57]([OH:66])(=[O:65])[C@@H:58]([C@H:60]([C:62]([OH:64])=[O:63])[OH:61])[OH:59]>CO.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.C#CCCCCCC.CCOCC>[OH:61][C@H:60]([C@@H:58]([OH:59])[C:57]([OH:66])=[O:65])[C:62]([OH:64])=[O:63].[CH3:1][O:2][C:3]([C@@:5]1([NH2:17])[CH2:9][CH2:8][C@H:7]([C:10]2[CH:15]=[CH:14][C:13]([C:19]#[C:20][CH3:21])=[CH:12][CH:11]=2)[CH2:6]1)=[O:4]

Participants

13

Reactant 7

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 8082PiperidineHCID 11776TriphenylphosphineHCID 123701-OctyneHCID 444305L-Tartaric acidHCID 24997352HCID 24997352, compound

Product 1

HCID 131729810HCID 131729810, compoundYield 72.6%

Reagents, catalysts & solvents 5

HCID 123701-OctyneCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 887MethanolSolvent2×HCID 3283Diethyl EtherSolvent

Conditions

Temperature
60 °C

Procedure

To a two-neck round bottom flask was added (1R,3S)-1-amino-3-(4-bromo-phenyl)-cyclopentanecarboxylic acid methyl ester; hydrochloride (3.94 g, 0.0118 mol), 1-octyne (3.48 mL, 0.0235 mol), triphenylphosphine (0.309 g, 0.00118 mol), piperidine (6.99 mL, 0.0706 mol), and THF (100 mL, 1 mol). The mixture was degassed, and Pd(PPh3)2Cl2 (0.41 g, 0.00059 mol) was added and the mixture was stirred for a few minutes under an atmosphere of nitrogen before addition of the copper(I) iodide (0.11 g, 0.00059 mol). The reaction was stirred under an atmosphere of nitrogen at 60° C. for 2 hours. More 1-octyne (12 mL, 0.081 mmol) was added in 3 portions. The reaction mixture was heated at 60° C. for a total of about 36 hours. The solvent was then removed and crude material was partitioned between EtOAc and saturated NaHCO3. The aqueous layer was back-extracted once with EtOAc. Organic layers were combined, dried over MgSO4 and the solvent was removed under reduced pressure. The residue was purified by silica gel chromatography using 1 L of EtOAc followed by 1 L of 2% MeOH in EtOAc to give 3.38 g crude product as a yellow oil. The crude product was dissolved in minimum amount of MeOH, to which L-tartaric acid (1.69 g) in MeOH was added. Ether was then added dropwise until solution just turned turbid. The mixture was left to crystallize. The solid was collected by filtration, washed with ether to give 3.91 g (72.6%) (1R,3S)-1-amino-3-(4-prop-1-ynyl-phenyl)-cyclopentanecarboxylic acid methyl ester; compound with (2R,3R)-2,3-dihydroxy-succinic acid.

Workup

  1. customThe mixture was degassed
  2. temperatureThe reaction mixture was heated at 60° C. for a total of about 36 hours
  3. customThe solvent was then removed
  4. customcrude material was partitioned between EtOAc and saturated NaHCO3
  5. extractionThe aqueous layer was back-extracted once with EtOAc
  6. dry with materialdried over MgSO4
  7. customthe solvent was removed under reduced pressure
  8. customThe residue was purified by silica gel chromatography
  9. customto give 3.38 g crude product as a yellow oil
  10. additionwas added
  11. waitThe mixture was left
  12. customto crystallize
  13. filtrationThe solid was collected by filtration
  14. washwashed with ether

Sources & evidence

ORD record
ord-3185799825f14d848ba4eb041bf82eb7
Source dataset
uspto-grants-2012_07
Patent number
US08217027B2

Reaction notes

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