Hexane → HCID 58017222, compound

HRID 661576Notes

Reaction equation

HRID 661576 reaction equation
[F:1][C:2]1[C:10]2[S:9][CH:8]=[CH:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.[Li]CCCC.CCCCCC.[C:22]([O:26][C:27]([N:29]1[CH2:33][CH2:32][C:31]([CH:41]=[O:42])([CH2:34][CH:35]2[CH2:40][CH2:39][O:38][CH2:37][CH2:36]2)[CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23]>O1CCCC1>[C:22]([O:26][C:27]([N:29]1[CH2:33][CH2:32][C:31]([CH:41]([C:8]2[S:9][C:10]3[C:2]([F:1])=[CH:3][CH:4]=[CH:5][C:6]=3[CH:7]=2)[OH:42])([CH2:34][CH:35]2[CH2:40][CH2:39][O:38][CH2:37][CH2:36]2)[CH2:30]1)=[O:28])([CH3:24])([CH3:25])[CH3:23]

Participants

6

Reactant 4

HCID 8058HexaneHCID 218660597-Fluoro-1-benzothiopheneHCID 58017286HCID 58017286, compoundHCID 178418339Butyllithium

Product 1

HCID 58017222HCID 58017222, compoundYield 30.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 7-fluoro-benzothiophene (0.22 g, 1.44 mmoles) in anhydrous tetrahydrofuran (10 ml) at −78° C. was added dropwise a solution of n-BuLi in hexane (1.6M, 0.9 ml, 1.44 mmoles). The reaction mixture was stirred at −78° C. for one hour, and then a solution of 3-formyl-3-(tetrahydro-pyran-4-ylmethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.3 g, 1.01 mmoles) in anhydrous tetrahydrofuran (5 ml) was then added. The reaction mixture was stirred at −78° C. for 3 hours, quenched with saturated aqueous ammonium chloride, and partitioned between ethyl acetate and saturated aqueous ammonium chloride solution. The organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (10 to 45% ethyl acetate in hexane) to yield 3-[(7-Fluoro-benzo[b]thiophen-2-yl)-hydroxy-methyl]-3-(tetrahydro-pyran-4-ylmethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester as a colorless semisolid (0.138 g, 30%). MS=450 [M+H]+.

Workup

  1. stirringThe reaction mixture was stirred at −78° C. for 3 hours
  2. customquenched with saturated aqueous ammonium chloride
  3. custompartitioned between ethyl acetate and saturated aqueous ammonium chloride solution
  4. washThe organic phase was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel chromatography (10 to 45% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-40ba733792a84929afc32c8cd0517b14
Source dataset
uspto-grants-2011_12
Patent number
US08084623B2

Reaction notes

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