Benzene → (1R,3R)-methyl 1-amino-3-(4-(3-(benzyloxy)prop-1-ynyl)phenyl)cyclopentanecarboxylate

HRID 1511845Notes

Reaction equation

HRID 1511845 reaction equation
[NH2:1][C@:2]1([C:14]([O:16][CH3:17])=[O:15])[CH2:6][CH2:5][C@@H:4]([C:7]2[CH:12]=[CH:11][C:10](Br)=[CH:9][CH:8]=2)[CH2:3]1.C(O)(=O)[C@@H]([C@H](C(O)=O)O)O.N1CCCCC1.[CH2:34]([O:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[C:35]#[CH:36].C1C=CC=CC=1>[Cu]I.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.C1COCC1>[NH2:1][C@:2]1([C:14]([O:16][CH3:17])=[O:15])[CH2:6][CH2:5][C@@H:4]([C:7]2[CH:12]=[CH:11][C:10]([C:36]#[C:35][CH2:34][O:37][CH2:38][C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)=[CH:9][CH:8]=2)[CH2:3]1

Participants

9

Reactant 5

HCID 241BenzeneHCID 8082PiperidineHCID 444305L-Tartaric acidHCID 6917484((Prop-2-yn-1-yloxy)methyl)benzeneHCID 25002100(1R,3R)-methyl 1-amino-3-(4-bromophenyl)cyclopentanecarboxylate

Product 1

HCID 57554604(1R,3R)-methyl 1-amino-3-(4-(3-(benzyloxy)prop-1-ynyl)phenyl)cyclopentanecarboxylateYield 86%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A round bottomed flask was charged with (1R,3R)-methyl 1-amino-3-(4-bromophenyl)cyclopentanecarboxylate, 0.5 L-tartaric acid 2 (30 g, 80 mmol), copper(I) iodide (0.153 g, 0.804 mmol), bis(triphenylphosphine)palladium(II) dichloride (2.82 g, 4.02 mmol) and THF (200 mL). The reaction mixture was purged with nitrogen. After about 15 minutes piperidine (35.8 mL, 362 mmol) and ((prop-2-ynyloxy)methyl)benzene (11.75 g, 80 mmol) were added and the reaction mixture was heated to about 65°. After about 2 hours additional (prop-2-ynyloxy)methyl)benzene (11.75 g, 80 mmol) was added. After about 8 hours the crude reaction mixture was partitioned between EtOAc and saturated NaHCO3. The organic layer was washed with brine, dried (Na2SO4) filtered, concentrated in vacuo and purified by flash chromatography on silica gel (eluting with EtOAC/Heptane followed by EtOAc/MeOH) to provide (1R,3R)-methyl 1-amino-3-(4-(3-(benzyloxy)prop-1-ynyl)phenyl)cyclopentanecarboxylate (25 g, 68.8 mmol, 86% yield) as a brown oil.

Workup

  1. customThe reaction mixture was purged with nitrogen
  2. temperaturethe reaction mixture was heated to about 65°
  3. customAfter about 8 hours the crude reaction mixture
  4. customwas partitioned between EtOAc and saturated NaHCO3
  5. washThe organic layer was washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. custompurified by flash chromatography on silica gel (eluting with EtOAC/Heptane followed by EtOAc/MeOH)

Sources & evidence

ORD record
ord-e84b1045d13a416da5c88ccc3405c1f2
Source dataset
uspto-grants-2012_07
Patent number
US08217027B2

Reaction notes

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