Cyclohexane → HCID 86730041, compound

HRID 2199473Notes

Reaction equation

HRID 2199473 reaction equation
[I:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=O)[CH2:7][CH2:6][CH2:5]2.C1CCCCC1.[CH3:19][O:20][CH2:21][C@@H:22]1[CH2:26][CH2:25][CH2:24][N:23]1[NH2:27].C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.O>[I:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[N:27][N:23]1[CH2:24][CH2:25][CH2:26][C@H:22]1[CH2:21][O:20][CH3:19])[CH2:7][CH2:6][CH2:5]2

Participants

8

Reactant 4

HCID 8078CyclohexaneHCID 516892Sodium BicarbonateHCID 7156993(S)-(-)-1-Amino-2-(methoxymethyl)pyrrolidineHCID 454898006-iodo-3,4-dihydronaphthalen-1(2H)-one

Product 1

HCID 86730041HCID 86730041, compoundYield 98.7%

Reagents, catalysts & solvents 3

HCID 521998p-Toluenesulfonic acid monohydrateCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred mixture of 6-iodo-3,4-dihydronaphthalen-1(2H)-one (I-8A, 20.90 g, 77 mmol), p-toluenesulfonic acid monohydrate (0.584 g, 3.07 mmol), and cyclohexane (40 mL) was added (S)-2-(methoxymethyl)pyrrolidin-1-amine (10 g, 77 mmol) dropwise at room temperature under nitrogen. The mixture was heated with azeotropic removal of water for 5 h. The reaction mixture was diluted with ethyl acetate (20 mL) and mixed with saturated aqueous sodium bicarbonate solution (15 mL). The aqueous layer was separated and extracted with ethyl acetate (2×30 mL). The combined organic solutions were dried over anhydrous sodium sulfate and concentrated under reduced pressure. Flash chromatography purification (330 g silica gel column, gradient elution from 0% to 20% EtOAc in hexanes) afforded (S)—N-(6-iodo-3,4-dihydronaphthalen-1(2H)-ylidene)-2-(methoxymethyl)pyrrolidin-1-amine (29.1 g, 76 mmol) as a yellow liquid. LC/MS M+1=385.

Workup

  1. customThe aqueous layer was separated
  2. extractionextracted with ethyl acetate (2×30 mL)
  3. dry with materialThe combined organic solutions were dried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customFlash chromatography purification (330 g silica gel column, gradient elution from 0% to 20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-1445f10207fe4433a9bd0f756acc0296
Source dataset
uspto-grants-2016_06
Patent number
US09359286B2

Reaction notes

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