Water → (R)-1-(5-tert-butoxy-2-isopropoxybenzo[d]thiazol-7-yl)-2-(1-(4-butoxyphenyl)-2-methylpropan-2-ylamino)ethanol

HRID 1426880Notes

Reaction equation

HRID 1426880 reaction equation
[C:1]([O:5][C:6]1[CH:7]=[C:8]([C@@H:19]2[CH2:21][O:20]2)[C:9]2[S:13][C:12]([O:14][CH:15]([CH3:17])[CH3:16])=[N:11][C:10]=2[CH:18]=1)([CH3:4])([CH3:3])[CH3:2].[CH2:22]([O:26][C:27]1[CH:32]=[CH:31][C:30]([CH2:33][C:34]([NH2:37])([CH3:36])[CH3:35])=[CH:29][CH:28]=1)[CH2:23][CH2:24][CH3:25].O.CC(OC)(C)C>CS(C)=O>[C:1]([O:5][C:6]1[CH:7]=[C:8]([C@@H:19]([OH:20])[CH2:21][NH:37][C:34]([CH3:35])([CH3:36])[CH2:33][C:30]2[CH:31]=[CH:32][C:27]([O:26][CH2:22][CH2:23][CH2:24][CH3:25])=[CH:28][CH:29]=2)[C:9]2[S:13][C:12]([O:14][CH:15]([CH3:17])[CH3:16])=[N:11][C:10]=2[CH:18]=1)([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 15413tert-Butyl methyl etherHCID 667439521-(4-Butoxyphenyl)-2-methylpropan-2-amineHCID 86696600(R)-5-tert-butoxy-2-isopropoxy-7-oxiranyl-benzothiazole

Product 1

HCID 86696597(R)-1-(5-tert-butoxy-2-isopropoxybenzo[d]thiazol-7-yl)-2-(1-(4-butoxyphenyl)-2-methylpropan-2-ylamino)ethanol

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

(R)-5-tert-butoxy-2-isopropoxy-7-oxiranyl-benzothiazole (145 g, 471.7 mmol) and 2-(4-butoxy-phenyl)-1,1-dimethyl-ethylamine (114.8 g, 518.9 mmol) were dissolved in DMSO (850 ml). The reaction mixture was heated to 80° C. and stirred for 27 h. The mixture was then cooled to 25° C. and added to a stirred mixture of water (1500 ml) and TBME (1500 ml). The aqueous layer was separated and extracted with TBME (1000 ml). The combined organic layers were sequentially washed with water (1500 ml) and brine (1000 ml), dried with anhydrous Na2SO4. After concentration, the residue was purified by column chromatography (eluting with 10% of EtOAc in n-heptane to 33% of EtOAc in n-heptane). Solid product (R)-1-(5-tert-butoxy-2-isopropoxybenzo[d]thiazol-7-yl)-2-(1-(4-butoxyphenyl)-2-methylpropan-2-ylamino)ethanol was obtained (140 g) as off-white solid.

Workup

  1. temperatureThe mixture was then cooled to 25° C.
  2. customThe aqueous layer was separated
  3. extractionextracted with TBME (1000 ml)
  4. washThe combined organic layers were sequentially washed with water (1500 ml) and brine (1000 ml)
  5. dry with materialdried with anhydrous Na2SO4
  6. concentrationAfter concentration
  7. customthe residue was purified by column chromatography (eluting with 10% of EtOAc in n-heptane to 33% of EtOAc in n-heptane)

Sources & evidence

ORD record
ord-a04d3363571946e6a2e9b5a298ae33e0
Source dataset
uspto-grants-2015_01
Patent number
US08933108B2

Reaction notes

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