Tetramethyltin → (r/s)-3-(Tert-butoxycarbonylamino)-1-(4-methyl-5-isoquinolinesulfonyl)pyrrolidine

HRID 1436026Notes

Reaction equation

HRID 1436026 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]1[CH2:13][CH2:12][N:11]([S:14]([C:17]2[C:18]3[C:19](Br)=[CH:20][N:21]=[CH:22][C:23]=3[CH:24]=[CH:25][CH:26]=2)(=[O:16])=[O:15])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:28][Sn](C)(C)C>CN(C)C=O.[Cl-].[Na+].O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6]([NH:8][CH:9]1[CH2:13][CH2:12][N:11]([S:14]([C:17]2[C:18]3[C:19]([CH3:28])=[CH:20][N:21]=[CH:22][C:23]=3[CH:24]=[CH:25][CH:26]=2)(=[O:16])=[O:15])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 2

HCID 11661TetramethyltinHCID 67242856(r/s)-3-(Tert-butoxycarbonylamino)-1-(4-bromo-5-isoquinolinesulfonyl)pyrrolidine

Product 1

HCID 67245257(r/s)-3-(Tert-butoxycarbonylamino)-1-(4-methyl-5-isoquinolinesulfonyl)pyrrolidine

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
120 °C

Procedure

A solution of Intermediate 1 (228 mg) obtained in Example 1, Step A and tetramethyltin (0.69 ml, Tokyo Kasei Kogyo) in N,N-dimethylformamide (4 ml) is added with tetrakis(triphenylphosphine)palladium(0) (29 mg, Kanto Chemicals), and the mixture is stirred at 120° C. with heating for 12 hours. The reaction mixture is cooled to room temperature, then added with saturated brine (5 ml), and extracted 3 times with ethyl acetate (5 ml for each time). The combined organic layer is washed with saturated brine (10 ml), and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure, and then the residue is purified by silica gel chromatography (n-hexane:ethyl acetate=1:1) to obtain the title compound (176 mg (predictive yield)).

Workup

  1. temperaturewith heating for 12 hours
  2. temperatureThe reaction mixture is cooled to room temperature
  3. extractionextracted 3 times with ethyl acetate (5 ml for each time)
  4. washThe combined organic layer is washed with saturated brine (10 ml)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent is evaporated under reduced pressure
  7. customthe residue is purified by silica gel chromatography (n-hexane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-3050e50eea124fcb8820bc54248f7772
Source dataset
uspto-grants-2009_11
Patent number
US07618984B2

Reaction notes

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