Dimethylformamide → 4[(1R)-2-({6-[4-(1,1-Dioxido-2,3-dihydro-1-benzothien-6-yl)butoxy]hexyl}amino)-1-hydroxyethyl]-2-(hydroxymethyl)phenol acetate

HRID 1593029Notes

Reaction equation

HRID 1593029 reaction equation
[NH2:1][CH2:2][C@@H:3]([C:5]1[CH:16]=[CH:15][C:8]2[O:9][C:10]([CH3:14])(C)[O:11][CH2:12][C:7]=2[CH:6]=1)[OH:4].BrCCCCCCO[CH2:25][CH2:26][CH2:27][C:28]1[CH:38]=[CH:37][C:31]2[CH2:32][CH2:33][S:34](=[O:36])(=[O:35])[C:30]=2[CH:29]=1.I[CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][O:46][CH2:47]CCC1C=CC2CCS(=O)(=O)C=2C=1.CN(C)C=[O:64]>>[C:10]([O:9][C:8]1[CH:15]=[CH:16][C:5]([C@@H:3]([OH:4])[CH2:2][NH:1][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][O:46][CH2:47][CH2:25][CH2:26][CH2:27][C:28]2[CH:38]=[CH:37][C:31]3[CH2:32][CH2:33][S:34](=[O:35])(=[O:36])[C:30]=3[CH:29]=2)=[CH:6][C:7]=1[CH2:12][OH:11])(=[O:64])[CH3:14]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 56600231(1R)-2-Amino-1-(2,2-dimethyl-4H-1,3-benzodioxin-6-YL)ethanolHCID 694453456-{3-[(6-Bromohexyl)oxy]propyl}-2,3-dihydro-1-benzothiophene 1,1-dioxideHCID 694477356-{3-[(6-Iodohexyl)oxy]propyl}-2,3-dihydro-1-benzothiophene 1,1-dioxide

Product 1

HCID 694429584[(1R)-2-({6-[4-(1,1-Dioxido-2,3-dihydro-1-benzothien-6-yl)butoxy]hexyl}amino)-1-hydroxyethyl]-2-(hydroxymethyl)phenol acetate

Conditions

Temperature
65 °C

Procedure

A mixture of (1R)-2-amino-1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)ethanol (112 mg) and 6-{3-[(6-bromohexyl)oxy]propyl}-2,3-dihydro-1-benzothiophene 1,1-dioxide and 6-{3-[(6-iodohexyl)oxy]propyl}-2,3-dihydro-1-benzothiophene 1,1-dioxide (370 mg) in dimethylformamide (1 ml) was allowed to stand at room temperature overnight. The solution was concentrated under reduced pressure and the residue was dissolved in ethanol and applied to an SCX-2 cartridge (10 g) eluting with ethanol and then with 10% aqueous ammonia in ethanol. The ammoniacal fractions were concentrated and the residue was dissolved in acetic acid (4 ml) and water (2 ml) and heated to 65° C. for 15 min. The solvents were removed under reduced pressure and the residue was purified on silica SPE cartridge (10 g) eluting with a gradient of 0-15% [10% ammonia in ethanol]-dichloromethane over 17 min. Appropriate fractions were combined and evaporated under reduced pressure. The residue was dissolved in acetic acid and then evaporated to dryness to give the title compound (59 mg) LCMS RT=2.32 min, ES+ve 506 (M+H)+.

Workup

  1. concentrationThe solution was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in ethanol
  3. washeluting with ethanol
  4. concentrationThe ammoniacal fractions were concentrated
  5. dissolutionthe residue was dissolved in acetic acid (4 ml)
  6. customThe solvents were removed under reduced pressure
  7. customthe residue was purified on silica SPE cartridge (10 g)
  8. washeluting with a gradient of 0-15% [10% ammonia in ethanol]-dichloromethane over 17 min
  9. customevaporated under reduced pressure
  10. dissolutionThe residue was dissolved in acetic acid
  11. customevaporated to dryness

Sources & evidence

ORD record
ord-e5d739a46eef42498c6f425511a7ad00
Source dataset
uspto-grants-2007_11
Patent number
US07294650B2

Reaction notes

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