Ammonium Hydroxide → (R)-tert-butyl 2-(5-methoxycarbonylthiophen-2-yl)pyrrolidine-1-carboxylate

HRID 564219

Reaction equation

HRID 564219 reaction equation
[C:1]([N:8]1[CH2:12][CH2:11][CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C1C[C@H]2N(C[C@H]3[C@@H]4CCCCN4C[C@@H]2C3)CC1.C([Li])(CC)C.Br[C:36]1[S:40][C:39]([C:41]([O:43][CH3:44])=[O:42])=[CH:38][CH:37]=1.F[B-](F)(F)F.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.[OH-].[NH4+]>COC(C)(C)C.C1CCCCC1.CCOCC.[Cl-].[Zn+2].[Cl-].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:44][O:43][C:41]([C:39]1[S:40][C:36]([C@H:12]2[CH2:11][CH2:10][CH2:9][N:8]2[C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])=[CH:37][CH:38]=1)=[O:42]

Participants

12

Reactant 6

HCID 14923Ammonium HydroxideHCID 605713Methyl 5-bromothiophene-2-carboxylateHCID 643455N-Boc-pyrrolidineHCID 644020SparteineHCID 44558591Tri-t-butylphosphine fluoroborateHCID 178418400CID 53628100

Product 1

HCID 66758892(R)-tert-butyl 2-(5-methoxycarbonylthiophen-2-yl)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 3007855ZincchlorideCatalystHCID 3283Diethyl EtherSolventHCID 8078CyclohexaneSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

To a solution of N-Boc-pyrrolidine (3 mL) and (−)-sparteine (3.9 mL) in tert-butyl methyl ether (36 mL) at −78° C. was added 1.4M sec-butyl lithium in cyclohexane (12.21 mL). The solution was stirred for 3 hours and 1M zinc chloride in ether (10.2 mL) was added. The mixture was stirred for 30 minutes and warmed to ambient temperature for 30 minutes. Methyl 5-bromothiophene-2-carboxylate (3.15 g), tri-tert-butylphosphine tetrafluoroborate (249 mg) and palladium(II) acetate (153 mg) were added, and the mixture was stirred at ambient temperature overnight, treated with concentrated ammonium hydroxide (1 mL) and stirred for 30 minutes, and filtered through diatomaceous earth (Celite®). The filtrate was washed with 0.5M hydrochloric acid solution and water and concentrated. The concentrate was flash chromatographed on silica gel with ethyl acetate/hexane.

Workup

  1. stirringThe mixture was stirred for 30 minutes
  2. stirringthe mixture was stirred at ambient temperature overnight
  3. stirringstirred for 30 minutes
  4. filtrationfiltered through diatomaceous earth (Celite®)
  5. washThe filtrate was washed with 0.5M hydrochloric acid solution and water
  6. concentrationconcentrated
  7. customchromatographed on silica gel with ethyl acetate/hexane

Sources & evidence

ORD record
ord-6c310ccc24894e758f571d8f23d9781f
Source dataset
uspto-grants-2011_11
Patent number
US08067613B2

Linked notes

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