102293-80-1

Usage

Uses

Used in Organic Synthesis:
Ethanone, 2-bromo-1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)is used as a key intermediate in organic synthesis for the production of various chemical compounds. Its unique structure allows for further functionalization and modification, making it a valuable component in the synthesis of complex organic molecules.
Used in Medicinal Chemistry:
In the field of medicinal chemistry, Ethanone, 2-bromo-1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)- serves as a precursor for the development of pharmaceuticals. Its structural features can be exploited to design and synthesize new drug candidates with potential therapeutic applications.
Used in Agrochemicals Production:
Ethanone, 2-bromo-1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)is also utilized in the production of agrochemicals, such as pesticides and herbicides. Its chemical properties can be harnessed to create effective agents for crop protection and management.
Used in Material Science:
Due to its chemical structure and properties, Ethanone, 2-bromo-1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)- may have potential applications in the development of new materials. Its unique characteristics can contribute to the creation of advanced materials with specific properties for various industries.
Used as a Research Chemical:
Ethanone, 2-bromo-1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)is employed as a research chemical for studying chemical reactions and mechanisms. Its reactivity and structural features make it an interesting subject for scientific investigations, contributing to the understanding of chemical processes and the development of new synthetic methods.
It is important to handle and use Ethanone, 2-bromo-1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)with care and according to safety guidelines due to its chemical nature.

Synthetic route

2-Methoxypropene (116-11-0) + 2-bromo-1-[4-hydroxy-3-(hydroxymethyl)-phenyl]ethanone (62932-94-9) → 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1)

Conditions	Yield
With toluene-4-sulfonic acid In dichloromethane at 0℃; for 0.666667h;	100%
With resin-SO3H In dichloromethane
With toluene-4-sulfonic acid In tetrahydrofuran at -10 - 10℃; for 1h;

2,2-dimethoxy-propane (77-76-9) + 2-bromo-1-[4-hydroxy-3-(hydroxymethyl)-phenyl]ethanone (62932-94-9) → 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1)

Conditions	Yield
With toluene-4-sulfonic acid In dichloromethane	99%
With toluene-4-sulfonic acid In dichloromethane at 20℃;	84%
In dichloromethane at 20℃; for 10h;	82%

1-(2,2-dimethyl-4H-benzo[d][1,3]dioxan-6-yl)ethanone (54030-34-1) → 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1)

Conditions	Yield
With bromine In diethyl ether at 10 - 15℃; for 2.33333h;	81.03%
Stage #1: 1-(2,2-dimethyl-4H-benzo[d][1,3]dioxan-6-yl)ethanone With sodium hexamethyldisilazane In tetrahydrofuran at -78℃; for 1h; Stage #2: With chloro-trimethyl-silane In tetrahydrofuran at -78℃; for 0.5h; Stage #3: With bromine In tetrahydrofuran at -78℃; for 1h;	57%
Stage #1: 1-(2,2-dimethyl-4H-benzo[d][1,3]dioxan-6-yl)ethanone With sodium hexamethyldisilazane In tetrahydrofuran at -75 - -70℃; for 1h; Stage #2: With chloro-trimethyl-silane; bromine In tetrahydrofuran at -75 - -70℃;	55%

4'-acetoxy-3'-(acetoxymethyl)acetophenone (24085-06-1) → 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: polyvinylpyridinium bromide perbromide resin / CH2Cl2 2: 1N HBr / tetrahydrofuran / 75 °C 3: resin-SO3H / CH2Cl2 View Scheme

3'-acetoxymethyl-4'-acetoxy-2-bromoacetophenone (24085-07-2) → 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1N HBr / tetrahydrofuran / 75 °C 2: resin-SO3H / CH2Cl2 View Scheme

4-Hydroxyacetophenone (99-93-4) → 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: resin-bound piperazinomethylpolystyrene / H2O; tetrahydrofuran 1.2: 14 percent / pTSA / toluene / 110 °C 2.1: polyvinylpyridinium bromide perbromide resin / CH2Cl2 3.1: 1N HBr / tetrahydrofuran / 75 °C 4.1: resin-SO3H / CH2Cl2 View Scheme

salicylaldehyde (90-02-8) → 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: aluminum (III) chloride / dichloromethane / 15 h / Reflux 2: sodium tetrahydroborate; acetic acid / 1 h / 10 °C 3: dichloromethane / 10 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: aluminum (III) chloride / dichloromethane / 0.5 h / 50 °C 1.2: 12 h / 40 °C 2.1: sodium tetrahydroborate; acetic acid / 0 - 20 °C / Inert atmosphere 3.1: toluene-4-sulfonic acid / dichloromethane / 20 °C View Scheme

5-(2-bromoacetyl)-2-hydroxybenzaldehyde (115787-50-3) → 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium tetrahydroborate; acetic acid / 1 h / 10 °C 2: dichloromethane / 10 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: sodium tetrahydroborate; acetic acid / 0 - 20 °C / Inert atmosphere 2: toluene-4-sulfonic acid / dichloromethane / 20 °C View Scheme

5-bromo-2-hydroxybenzyl alcohol (2316-64-5) → 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: acetone 2: n-butyllithium / tetrahydrofuran 3: sodium hexamethyldisilazane / tetrahydrofuran 4: bromine View Scheme
Multi-step reaction with 3 steps 1.1: aluminum (III) chloride / tetrahydrofuran / 1 h / 0 - 30 °C / Inert atmosphere 2.1: n-butyllithium / tetrahydrofuran / 1 h / -75 - -70 °C 2.2: -75 - -70 °C 3.1: sodium hexamethyldisilazane / tetrahydrofuran / 1 h / -75 - -70 °C 3.2: -75 - -70 °C View Scheme
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / N,N-dimethyl-formamide / 20 °C 2.1: n-butyllithium / hexane; tetrahydrofuran / 1 h / -78 °C / Inert atmosphere 2.2: 4 h / -78 °C / Inert atmosphere 3.1: sodium hexamethyldisilazane / tetrahydrofuran / 1 h / -78 °C 3.2: 1 h / -78 °C 3.3: 1 h / -78 °C View Scheme

6-bromo-2,2-dimethyl-4H-benzo[1,3]dioxine (52113-69-6) → 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: n-butyllithium / tetrahydrofuran 2: sodium hexamethyldisilazane / tetrahydrofuran 3: bromine View Scheme
Multi-step reaction with 2 steps 1.1: n-butyllithium / tetrahydrofuran / 1 h / -75 - -70 °C 1.2: -75 - -70 °C 2.1: sodium hexamethyldisilazane / tetrahydrofuran / 1 h / -75 - -70 °C 2.2: -75 - -70 °C View Scheme
Multi-step reaction with 2 steps 1.1: n-butyllithium / hexane; tetrahydrofuran / 1 h / -78 °C / Inert atmosphere 1.2: 4 h / -78 °C / Inert atmosphere 2.1: sodium hexamethyldisilazane / tetrahydrofuran / 1 h / -78 °C 2.2: 1 h / -78 °C 2.3: 1 h / -78 °C View Scheme

C15H22O3Si → 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1)

Conditions	Yield
With bromine

5-bromosalicyclaldehyde (1761-61-1) → 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sodium tetrahydroborate; ethanol / 5 h / 0 - 20 °C 2.1: toluene-4-sulfonic acid / N,N-dimethyl-formamide / 20 °C 3.1: n-butyllithium / hexane; tetrahydrofuran / 1 h / -78 °C / Inert atmosphere 3.2: 4 h / -78 °C / Inert atmosphere 4.1: sodium hexamethyldisilazane / tetrahydrofuran / 1 h / -78 °C 4.2: 1 h / -78 °C 4.3: 1 h / -78 °C View Scheme

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → 2-azido-1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)ethanone (384340-05-0)

Conditions	Yield
With sodium azide In N,N-dimethyl-formamide at 20 - 30℃; for 2h;	97%
With sodium azide In N,N-dimethyl-formamide at 20℃; for 2h;	95%
With sodium azide In N,N-dimethyl-formamide at 20℃; for 2h;	89%
With sodium azide In DMF (N,N-dimethyl-formamide) at 20℃; for 2h;
With sodium azide In DMF (N,N-dimethyl-formamide) at 20℃; for 2h;

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → (R)-2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanol

Conditions	Yield
With sodium formate; η5-pentamethylcyclopentadienylrhodium dimer In water at 20℃; for 12h;	93%
With 2-(morpholin-4-yl)ethanol; β-nicotinamide adenine dinucleotide phosphate disodium salt; alcohol dehydrogenase CDX-005; nitric acid In water; dimethyl sulfoxide; isopropyl alcohol at 25℃; for 24h; Reagent/catalyst; Solvent; Large scale; Enzymatic reaction;	86.7%
With (1R,2S)-1-Amino-2-indanol; dimethyl sulfide borane In tetrahydrofuran at 20 - 25℃; for 3.5h;	76.12%

tert-butylamine (75-64-9) + 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → C16H23NO3

Conditions	Yield
With potassium carbonate In tetrahydrofuran; water	93%

(2S)-2-phenylglycinol (20989-17-7) + 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → (1'S)-1-(2,2-dimethyl-4H-benzo[1,3]dioxin-6-yl)-2-(2-hydroxy-1-phenyl-ethylamino)-ethanone (380414-67-5)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran for 4h;	80%
With resin-N(iPr)2 In tetrahydrofuran

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → (R)-2-Bromo-1-(2,2-dimethyl-4H-benzo[1,3]dioxin-6-yl)ethanol (956234-46-1)

Conditions	Yield
Stage #1: 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone With sodium tetrahydroborate In methanol at 0℃; for 0.5h; Stage #2: With ammonium chloride In methanol; water at 0℃;	79%
With sodium tetrahydroborate In methanol at 0 - 20℃; for 1h;

C27H35N3O3 + 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → 2-(4-(benzyl(2-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)-2-oxoethyl)amino)butyl)-4-(3,4-dimethoxyphenyl)-4a,5,6,7,8,8a-hexahydrophthalazin-1(2H)-one

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 12h;	71%

C28H37N3O3 + 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → 2-(5-(benzyl(2-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)-2-oxoethyl)amino)pentyl)-4-(3,4-dimethoxyphenyl)-4a,5,6,7,8,8a-hexahydrophthalazin-1(2H)-one

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 12h;	70%

C29H39N3O3 + 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → 2-(6-(benzyl(2-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)-2-oxoethyl)amino)hexyl)-4-(3,4-dimethoxyphenyl)-4a,5,6,7,8,8a-hexahydrophthalazin-1(2H)-one

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 12h;	68%

C25H31N3O3 + 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → cis-2-(3-(benzyl(2-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)-2-oxoethyl)amino)propyl)-4-(3,4-dimethoxyphenyl)-4a,5,6,7,8,8a-hexahydrophthalazin-1(2H)-one

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 12h;	65%

(S)-2-methoxy-1-phenylethylamine (91298-74-7) + 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → 1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-[(1S)-2-methoxy-1-phenylethylamino]ethanone (500317-68-0)

Conditions	Yield
With polystyryldiisopropylethylamine In tetrahydrofuran for 2h;	64%

iminodicarboxylic acid di-tert-butyl ester (51779-32-9) + 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → di-(tert-butyl) 2-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-oxoethyliminodicarbonate (452339-70-7)

Conditions	Yield
With caesium carbonate In acetonitrile at 20 - 25℃; for 6h; Inert atmosphere;	64%
With caesium carbonate In acetonitrile at 21℃; for 24h;	28%
With caesium carbonate In acetonitrile at 21℃; for 24h;

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → (R)-(-)-salmeterol

Conditions	Yield
Multi-step reaction with 7 steps 1: 28 percent / Cs2CO3 / acetonitrile / 24 h / 21 °C 2: 43 percent / CF3CO2H / CH2Cl2 / 4 h / 20 °C 3: 99 percent / (R)-tetrahydro-1-Me-3,3-Ph2-1H,3H-pyrrolo[1,2-c][1,3-2]oxaza; borole; BH3*THF / toluene / 5 - 20 °C 4: 70 percent / NaH / dimethylformamide / 3 h / 20 °C 5: 77 percent / NaH / dimethylformamide / 4 h / 5 - 20 °C 6: 96 percent / KOSiMe3 / tetrahydrofuran / 1 h / Heating 7: 80 percent / AcOH; MeOH / 72 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: resin-N(iPr)2 / tetrahydrofuran 2.1: CaCl2 / methanol / 0.17 h / 0 °C 2.2: 76 percent / resin-NMe3(1+)*BH4(1-) / methanol / 2 h / 0 - 20 °C 3.1: (polystyrylmethyl)trimethylammonium cyanoborohydride; AcOH / CH2Cl2 3.2: 98 percent / resin-NMe3(1+)*NaCO3(1-) / CH2Cl2 4.1: H2 / Pd(OH)2/C / ethyl acetate / 2 h 4.2: 87 percent / SCX-2 View Scheme

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → (R)-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)-2-(6-(4-phenylbutoxy)hexylamino)ethanol (590410-69-8)

Conditions	Yield
Multi-step reaction with 6 steps 1: 28 percent / Cs2CO3 / acetonitrile / 24 h / 21 °C 2: 43 percent / CF3CO2H / CH2Cl2 / 4 h / 20 °C 3: 99 percent / (R)-tetrahydro-1-Me-3,3-Ph2-1H,3H-pyrrolo[1,2-c][1,3-2]oxaza; borole; BH3*THF / toluene / 5 - 20 °C 4: 70 percent / NaH / dimethylformamide / 3 h / 20 °C 5: 77 percent / NaH / dimethylformamide / 4 h / 5 - 20 °C 6: 96 percent / KOSiMe3 / tetrahydrofuran / 1 h / Heating View Scheme
Multi-step reaction with 4 steps 1: 80 percent / i-Pr2NEt / tetrahydrofuran / 4 h 2: 76 percent / CaCl2*2H2O; NaBH4 / methanol / 2 h / 0 °C 3: 87 percent / sodium triacetoxyborohydride / CH2Cl2 / 18 h 4: 87 percent / H2 / aq. Pd(OH)2/C / ethanol / 18 h View Scheme

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → (5R)-5-(2,2-dimethyl- 4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one (452339-73-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: 28 percent / Cs2CO3 / acetonitrile / 24 h / 21 °C 2: 43 percent / CF3CO2H / CH2Cl2 / 4 h / 20 °C 3: 99 percent / (R)-tetrahydro-1-Me-3,3-Ph2-1H,3H-pyrrolo[1,2-c][1,3-2]oxaza; borole; BH3*THF / toluene / 5 - 20 °C 4: 70 percent / NaH / dimethylformamide / 3 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1: caesium carbonate / acetonitrile / 6 h / 20 - 25 °C / Inert atmosphere 2: trifluoroacetic acid / dichloromethane / 5 h / 10 - 25 °C 3: dimethylsulfide borane complex; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran; toluene / 1 h / -10 °C 4: potassium tert-butylate / N,N-dimethyl-formamide / 1 h / 10 - 20 °C View Scheme
Multi-step reaction with 4 steps 1: caesium carbonate / acetonitrile / 20 °C 2: trifluoroacetic acid / dichloromethane / 2 h / 10 °C 3: (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole; dimethylsulfide borane complex / toluene; tetrahydrofuran / 0.67 h / -10 °C / Inert atmosphere 4: potassium tert-butylate / N,N-dimethyl-formamide / 3 h / 0 - 20 °C / Inert atmosphere View Scheme

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → tert-butyl 2-(2,2-dimethyl-4H-1,3-benzodioxane-6-yl)-2-carbonylethylcarbamate (452339-71-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 28 percent / Cs2CO3 / acetonitrile / 24 h / 21 °C 2: 43 percent / CF3CO2H / CH2Cl2 / 4 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: caesium carbonate / acetonitrile / 6 h / 20 - 25 °C / Inert atmosphere 2: trifluoroacetic acid / dichloromethane / 5 h / 10 - 25 °C View Scheme
Multi-step reaction with 2 steps 1: caesium carbonate / acetonitrile / 20 °C 2: trifluoroacetic acid / dichloromethane / 2 h / 10 °C View Scheme

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → tert-butyl (2R)-2-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-hydroxyethylcarbamate (452339-72-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 28 percent / Cs2CO3 / acetonitrile / 24 h / 21 °C 2: 43 percent / CF3CO2H / CH2Cl2 / 4 h / 20 °C 3: 99 percent / (R)-tetrahydro-1-Me-3,3-Ph2-1H,3H-pyrrolo[1,2-c][1,3-2]oxaza; borole; BH3*THF / toluene / 5 - 20 °C View Scheme
Multi-step reaction with 3 steps 1: caesium carbonate / acetonitrile / 6 h / 20 - 25 °C / Inert atmosphere 2: trifluoroacetic acid / dichloromethane / 5 h / 10 - 25 °C 3: dimethylsulfide borane complex; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran; toluene / 1 h / -10 °C View Scheme
Multi-step reaction with 3 steps 1: caesium carbonate / acetonitrile / 20 °C 2: trifluoroacetic acid / dichloromethane / 2 h / 10 °C 3: (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole; dimethylsulfide borane complex / toluene; tetrahydrofuran / 0.67 h / -10 °C / Inert atmosphere View Scheme

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → (5R)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-3-[6-(4-phenylbutoxy)hexyl]-1,3-oxazolidin-2-one (590410-68-7)

Conditions	Yield
Multi-step reaction with 5 steps 1: 28 percent / Cs2CO3 / acetonitrile / 24 h / 21 °C 2: 43 percent / CF3CO2H / CH2Cl2 / 4 h / 20 °C 3: 99 percent / (R)-tetrahydro-1-Me-3,3-Ph2-1H,3H-pyrrolo[1,2-c][1,3-2]oxaza; borole; BH3*THF / toluene / 5 - 20 °C 4: 70 percent / NaH / dimethylformamide / 3 h / 20 °C 5: 77 percent / NaH / dimethylformamide / 4 h / 5 - 20 °C View Scheme

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → 1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-[(1S)-2-methoxy-1-phenylethylamino]ethanol

Conditions	Yield
Multi-step reaction with 2 steps 1: 64 percent / polystyryldiisopropylethylamine / tetrahydrofuran / 2 h 2: 91 percent / CaCl2; polystyryl(trimethyl)ammonium borohydride / methanol / 2 h / 0 - 20 °C View Scheme

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → (1S)-1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-[(1S)-2-hydroxy-1-phenylethylamino]ethanol

Conditions	Yield
Multi-step reaction with 2 steps 1: 80 percent / i-Pr2NEt / tetrahydrofuran / 4 h 2: CaCl2*2H2O; NaBH4 / methanol / 2 h / 0 °C View Scheme

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → (1R,1'S)-1-(2,2-dimethyl-4H-benzo[1,3]dioxin-6-yl)-2-(2-hydroxy-1-phenyl-ethylamino)-ethanol (380414-68-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 80 percent / i-Pr2NEt / tetrahydrofuran / 4 h 2: 76 percent / CaCl2*2H2O; NaBH4 / methanol / 2 h / 0 °C View Scheme
Multi-step reaction with 2 steps 1.1: resin-N(iPr)2 / tetrahydrofuran 2.1: CaCl2 / methanol / 0.17 h / 0 °C 2.2: 76 percent / resin-NMe3(1+)*BH4(1-) / methanol / 2 h / 0 - 20 °C View Scheme

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → (4S)-3-[2-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-hydroxyethyl]-4-phenyl-1,3-oxazolidin-2-one

Conditions	Yield
Multi-step reaction with 3 steps 1: 80 percent / i-Pr2NEt / tetrahydrofuran / 4 h 2: 91 percent / CH2Cl2 / 0.25 h 3: 87 percent / CaCl2; polystyryl(trimethyl)ammonium borohydride / methanol / 2 h / 0 - 20 °C View Scheme

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → (4S)-3-[2-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-oxoethyl]-4-phenyl-1,3-oxazolidin-2-one (500317-72-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 80 percent / i-Pr2NEt / tetrahydrofuran / 4 h 2: 91 percent / CH2Cl2 / 0.25 h View Scheme

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → (1R,1'S)-1-(2,2-dimethyl-4H-benzo[1,3]dioxin-6-yl)-2-{(2-hydroxy-1-phenyl-ethyl)-[6-(4-phenyl-butoxy)-hexyl]-amino}-ethanol (380414-69-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 80 percent / i-Pr2NEt / tetrahydrofuran / 4 h 2: 76 percent / CaCl2*2H2O; NaBH4 / methanol / 2 h / 0 °C 3: 87 percent / sodium triacetoxyborohydride / CH2Cl2 / 18 h View Scheme
Multi-step reaction with 3 steps 1.1: resin-N(iPr)2 / tetrahydrofuran 2.1: CaCl2 / methanol / 0.17 h / 0 °C 2.2: 76 percent / resin-NMe3(1+)*BH4(1-) / methanol / 2 h / 0 - 20 °C 3.1: (polystyrylmethyl)trimethylammonium cyanoborohydride; AcOH / CH2Cl2 3.2: 98 percent / resin-NMe3(1+)*NaCO3(1-) / CH2Cl2 View Scheme

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → 2-{bis-[6-(4-phenyl-butoxy)-hexyl]-amino}-1-(2,2-dimethyl-4H-benzo[1,3]dioxin-6-yl)-ethanol

Conditions	Yield
Multi-step reaction with 3 steps 1.1: resin-N(iPr)2 / tetrahydrofuran 2.1: CaCl2 / methanol / 0.17 h / 0 °C 2.2: 76 percent / resin-NMe3(1+)*BH4(1-) / methanol / 2 h / 0 - 20 °C 3.1: H2 / Pd(OH)2/C / ethyl acetate View Scheme

Upstream product

• 116-11-0 2-Methoxypropene 
• 62932-94-9 2-bromo-1-[4-hydroxy-3-(hydroxymethyl)-phenyl]ethanone 
• 77-76-9 2,2-dimethoxy-propane 
• 2316-64-5 5-bromo-2-hydroxybenzyl alcohol 
• 52113-69-6 6-bromo-2,2-dimethyl-4H-benzo[1,3]dioxine 
• 1761-61-1 5-bromosalicyclaldehyde 
• 115787-50-3 5-(2-bromoacetyl)-2-hydroxybenzaldehyde 
• 90-02-8 salicylaldehyde 
• 54030-34-1 1-(2,2-dimethyl-4H-benzo[d][1,3]dioxan-6-yl)ethanone 
• 99-93-4 4-Hydroxyacetophenone 
• 24085-07-2 3'-acetoxymethyl-4'-acetoxy-2-bromoacetophenone 
• 24085-06-1 4'-acetoxy-3'-(acetoxymethyl)acetophenone 

Downstream Products

• 380414-67-5 (1'S)-1-(2,2-dimethyl-4H-benzo[1,3]dioxin-6-yl)-2-(2-hydroxy-1-phenyl-ethylamino)-ethanone 
• 500317-68-0 1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-[(1S)-2-methoxy-1-phenylethylamino]ethanone 
• 452339-70-7 di-(tert-butyl) 2-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-oxoethyliminodicarbonate 
• 530118-35-5 C₃₅H₃₆BrNO₅ 
• 457658-56-9 3-[2-(4-{[6-({(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl}amino)hexyl]oxy}butyl)phenyl]-2,4-imidazolidinedione acetic acid salt 
• 457645-16-8 3-[4-(4-{[6-({(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phen yl]ethyl}amino)hexyl]oxy}butyl)phenyl]-2,4-imidazolidinedione acetic acid salt 
• 457658-71-8 3-[3-(4-{[6-({(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl}amino)hexyl]oxy}butyl)phenyl]-5,5-dimethyl-2,4-imidazolidinedione acetic acid salt 
• 457658-58-1 3-{[3-(4-{[6-({(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl}amino) hexyl]oxy}butyl)phenyl]methyl}-2,4-imidazolidinedione acetic acid salt 
• 457658-85-4 1-{[3-(4-{[6-({(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl}amino) hexyl]oxy}butyl)phenyl]methyl}-2,4-imidazolidinedione acetic acid salt 
• 457658-83-2 2-{3-[3-(4-{[6-({(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl}amino)hexyl]oxy}butyl)phenyl]-2,5-dioxo-1-imidazolidinyl}acetamide acetic acid salt 
• 671777-24-5 3-[3-(4-{[6-({(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl}amino)hexyl]oxy}butyl)phenyl]-2,4(1H,3H)-pyrimidinedione acetic acid salt 
• 671777-19-8 1-[3-(4-{[6-({(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl}amino)hexyl]oxy}butyl)phenyl]-2,4(1H,3H)-pyrimidinedione acetic acid salt 
• 594860-94-3 N-({[3-(4-{[6-({(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl}amino)hexyl]oxy}butyl)phenyl]amino}carbonyl)glycine acetic acid salt 
• 457631-24-2 3-(3-{4-[(6-{[(2R)-2-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-hydroxyethyl]amino}hexyl)oxy]butyl}phenyl)imidazolidine-2,4-dione 

Relevant academic research and scientific papers

A convenient synthesis of (R)-salmeterol via Rh-catalyzed asymmetric transfer hydrogenation

(R)-Salmeterol was synthesized in eight steps with salicaldehyde as the starting material. The key chiral intermediate, alcohol 5, was prepared via Rh-catalyzed asymmetric transfer hydrogenation with (S,S)-PEG-BsDPEN or (S,S)-TsDPEN ligand and sodium formate as the hydrogen donor under mild conditions.

Preparation method of leverbuterol and its salt

The invention provides a method for cheap and effective preparation of leverbuterol in industry. The method consists of: taking protected 4-hydroxy-3-hydroxymethyl acetophenone as the raw material to react with bromine to generate acyl or alkyl protected 4-hydroxy-3-hydroxymethyl bromoacetophenone, under in the presence of (1R, 2S)-(+)-indanol as a catalyst, using borane to conduct chiral reduction on carbonyl in the structural formula to obtain R configuration acyl or alkyl protected 4-hydroxy-3-hydroxymethyl alpha bromo phenethyl alcohol, then carrying out reaction with tert-butylamine to generate acyl or alkyl protected 4-hydroxy-3-hydroxymethyl phenylaminoethanol, and finally removing the acyl protecting group to obtain leverbuterol free alkali, and letting the free alkali and acid form a salt. The finished product has optical purity up to 99.9%, and no other chiral resolution way is needed for purification.

Phenylethanolamine derivative and its preparation method and application

The invention relates to a phenylethanolamine derivative represented in the following formula 1. The phenylethanolamine derivative can serve as a beta 2 receptor agonist. The formula can be seen from the description.

Levalbuterol intermediate and synthetic method of levalbuterol hydrochloride

The invention provides a levalbuterol intermediate and a levalbuterol hydrochloride synthesis method, and relates to a levalbuterol intermediate and a method for preparing levalbuterol hydrochloride from the intermediate. The method comprises steps as follows: 2-halogenate-1-(2,2-dimelthyl-4-hydrogen-benzo [d][1,3] dioxane)-butanone and organic amine have a Hoffman alkylation reaction to prepare a compound in the formula 2, the structural formula of the compound is shown in the specification, and the compound in the formula 2 is subjected to a reduction reaction, optically pure organic acid resolution and deprotection by hydrochloric acid to obtain levalbuterol hydrochloride. The method does not need processes of protection or deprotection and the like of hydroxyl groups on a benzene ring, protection, deprotection and purification processes are reduced, the synthesis route is short, operation is simple, meanwhile, borane-thioether does not need to be used as a reduction agent, and safety and environmental protection are realized.

METHOD OF PREPARING INTERMEDIATE OF SALMETEROL

A method of preparing an intermediate of salmeterol (Compound 1, 2-amino-1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl) ethanol) includes: reacting compound 2 with 2-methoxypropene in a first organic solvent to produce a reaction solution including compound 3, compound 2 including a 2-bromo precursor of Compound 1; reacting compound 3 with a nitrogen source to produce compound 4; reacting compound 4 with sodium borohydride in a second organic solvent to produce compound 5; and debenzylating compound 5 by ammonium formate / palladium-carbon catalytic transfer hydrogenation in a third organic solvent to produce Compound 1. A method of preparing salmeterol includes preparing Compound 1, and reacting Compound 1 to prepare salmeterol.

PROCESS FOR THE PREPARATION OF VILANTEROL AND INTERMEDIATES THEREOF

An improved process for the preparation of vilanterol and pharmaceutically acceptable salts thereof is disclosed. More specifically the improved process for preparing intermediates for the preparation of vilanterol is disclosed.

Multivalent design of long-acting β2-adrenoceptor agonists incorporating biarylamines

A series of potent β2-adrenoceptor agonists incorporating a biarylamine secondary binding group was identified. The previously reported milveterol (5), identified by a multivalent approach and containing a typical β2-agonist primary binding group linked via a phenethylamine linker to a hydrophilic secondary binding group, served as an initiation point. A more hydrophobic set of secondary binding groups was explored, prepared rapidly from a common intermediate by Buchwald-Hartwig amination. TD-5471 (25), a potent and selective full agonist of the human β2- adrenoceptor, was identified as the most promising agent. It is potent, with slow onset in an in vitro guinea pig trachea model and shows a dose-dependent and long duration of action in an in vivo guinea pig model of bronchoprotection. TD-5471 is structurally differentiated from milveterol and its long duration of action is consistent with a correlation with hydrophobicity observed in other long-acting β2-agonist discovery programs.

Hybrids consisting of the pharmacophores of salmeterol and roflumilast or phthalazinone: Dual β2-adrenoceptor agonists-PDE4 inhibitors for the treatment of COPD

A novel class of dual pharmacology bronchodilators targeting both β2-adrenoceptor and PDE4 was designed and synthesised by combining the pharmacophores of salmeterol and roflumilast or phthalazinone. All the compounds exhibited better β2-adrenoceptor agonist activities (pEC50 = 8.47-9.20) than the reference compound salmeterol (pEC50 = 8.3) and good inhibitory activity on PDE4B2 (IC 50 = 0.235-1.093 μM).

SUBSTITUTED ETHANOLAMINES

The present invention relates to new substituted ethanolamine adrenergic receptor modulators, pharmaceutical compositions thereof, and methods of use thereof.

Compounds having beta adrenergic receptor agonist and muscarinic receptor antagonist activity

This invention provides compounds of formula I: wherein R1, R2, R4, R5, R6, R7, R8a, R8b, W, a, b, c and m are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The compounds of this invention possess both β2 adrenergic receptor agonist and muscarinic receptor antagonist activity. Accordingly, such compounds are expected to be useful as therapeutic agents for treating pulmonary disorders, such as chronic obstructive pulmonary disease and asthma.