43229-01-2

Basic information

• Product Name: 2-Bromo-4'-Benzyloxy-3'-nitroacetophenone
• Synonyms: ALPHA-BROMO 4-BENZYLOXY-3-NITRO ACETOPHENONE;2-BROMO-4'-BENZYLOXY-3'-NITROACETOPHENONE;2-Bromo-1-[3-Nitro-4-(Phenylmethoxy)Phenyl]Ethanone;2-Bromo-1-[3-nitro-4-(phenylmethoxy)phenyl]-ethanone;Formoterol Intermediate;1-(4-BENZYLOXY-3-NITRO-PHENYL)-2-BROMO-ETHANONE;2-BROMO-4''-BENZYLLOXY-3''-NITROACETOPHENONE;2-bromo-1-(4-benzyloxy-3-nitrophenyl)ethanone
• CAS NO: 43229-01-2
• Molecular Formula: C₁₅H₁₂BrNO₄
• Molecular Weight: 350.16
• EINECS: 1592732-453-0
• Mol File: 43229-01-2.mol
• Article Data: 13

Chemical Properties

• Melting Point: 135-137 °C(Solv: ethanol (64-17-5))
• Boiling Point: 465.239 °C at 760 mmHg
• Flash Point: 235.168 °C
• Appearance: /
• Density: 1.518 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.627
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility: Soluble in Methylene chloride, sparingly soluble in ethyl acetate, insoluble in water
• CAS DataBase Reference: 2-Bromo-4'-Benzyloxy-3'-nitroacetophenone(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Bromo-4'-Benzyloxy-3'-nitroacetophenone(43229-01-2)
• EPA Substance Registry System: 2-Bromo-4'-Benzyloxy-3'-nitroacetophenone(43229-01-2)

Safety Data

• Hazardous Substances Data: 43229-01-2(Hazardous Substances Data)

Usage

Uses

1-(4-(Benzyloxy)-3-nitrophenyl)-2-bromoethanone, can be used as an intermediate in the synthesis of Arformoterol Tartrate (A767505), which is a derivative of Arformoterol, a long acting beta-adrenoceptor agonist drug indicated for the treatment of chronic obstructive pulmonary disease (COPD).

InChI:InChI=1/C15H12BrNO4/c16-9-14(18)12-6-7-15(13(8-12)17(19)20)21-10-11-4-2-1-3-5-11/h1-8H,9-10H2

Synthetic route

4-benzyloxy-3-nitroacetophenone (14347-05-8) → 4-benzyloxy-3-nitrophenacyl bromide (43229-01-2)

Conditions	Yield
With N,N,N-trimethylanilinium bromide In dichloromethane at 300℃; for 4h;	98%
With phenyltrimethylammonium tribromide In methanol; dichloromethane at 20℃;	97%
With bromine; acetic acid at 20℃;	85%

4'-hydroxy-3'-nitroacetophenone (6322-56-1) → 4-benzyloxy-3-nitrophenacyl bromide (43229-01-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: TBAI, K2CO3 / acetone 2: Br2 / CHCl3 View Scheme
Multi-step reaction with 2 steps 1.1: N-ethyl-N,N-diisopropylamine / acetonitrile / 20 °C 1.2: 3 h / 20 °C / Reflux 2.1: tetra-N-butylammonium tribromide / tetrahydrofuran; methanol / 4 h View Scheme
Multi-step reaction with 2 steps 1.1: potassium carbonate / water; acetone / 20 °C 1.2: 17 h / Reflux 2.1: bromine / acetic acid / 20 °C View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / acetone; water / 60 °C 2: bromine / acetic acid / 20 °C View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate; sodium iodide / acetone / 66 h / Heating / reflux 2: phenyltrimethylammonium tribromide / tetrahydrofuran / 12 h / 20 °C View Scheme

4-Hydroxyacetophenone (99-93-4) → 4-benzyloxy-3-nitrophenacyl bromide (43229-01-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: HNO3 / acetic acid / 0 °C 2: TBAI, K2CO3 / acetone 3: Br2 / CHCl3 View Scheme
Multi-step reaction with 3 steps 1: HNO3 / acetic acid / -0.1 °C 2: TBAI, K2CO3 / acetone 3: Br2 / CHCl3 View Scheme

benzyl bromide (100-39-0) → 4-benzyloxy-3-nitrophenacyl bromide (43229-01-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: N-ethyl-N,N-diisopropylamine / acetonitrile / 20 °C 1.2: 3 h / 20 °C / Reflux 2.1: tetra-N-butylammonium tribromide / tetrahydrofuran; methanol / 4 h View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate; sodium iodide / acetone / 66 h / Heating / reflux 2: phenyltrimethylammonium tribromide / tetrahydrofuran / 12 h / 20 °C View Scheme

benzyl chloride (100-44-7) → 4-benzyloxy-3-nitrophenacyl bromide (43229-01-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: potassium carbonate / water; acetone / 20 °C 1.2: 17 h / Reflux 2.1: bromine / acetic acid / 20 °C View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / acetone; water / 60 °C 2: bromine / acetic acid / 20 °C View Scheme

4'-hydroxy-3'-nitroacetophenone (6322-56-1) + benzyl chloride (100-44-7) → 4-benzyloxy-3-nitrophenacyl bromide (43229-01-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium carbonate; N-benzyl-N,N,N-triethylammonium chloride / N,N-dimethyl-formamide / 4 h / 115 - 120 °C 2: 2,2'-azobis(isobutyronitrile); bromine / 4 h / 38 - 42 °C View Scheme

4-benzyloxy-3-nitrophenacyl bromide (43229-01-2) → (R)-2-bromo-1-(4-benzyloxy-3-nitrophenyl)ethanol (188690-82-6)

Conditions	Yield
With dimethylsulfide borane complex; (3aS-cis)-(-)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]oxazole-2-isopropylborane In tetrahydrofuran at -5 - 5℃; for 0.5h; Solvent; Temperature;	99%
With oxazaborolidine from cis (1R,2S)-aminoindanol and trimethylboroxine; borane In tetrahydrofuran at -15℃;	98%
With borane N,N-diethylaniline complex; (1R,2S)-1-Amino-2-indanol In tetrahydrofuran at 3 - 5℃; for 3.5h; optical yield given as %ee;	95%

4-benzyloxy-3-nitrophenacyl bromide (43229-01-2) → (S)-1-(4-(benzyloxy)-3-nitrophenyl)-2-bromoethanol (193761-53-4)

Conditions	Yield
With oxazaborolidine from cis (1S,2R)-aminoindanol and trimethylboroxine; borane In tetrahydrofuran at -15℃;	98%
With borane N,N-diethylaniline complex; (1S,2R)-1-amino-2-indanol In tetrahydrofuran at 0 - 5℃; for 2h;	94%
With borane N,N-diethylaniline complex; (1S,2R)-1-amino-2-indanol In tetrahydrofuran at 0 - 5℃; for 2h;	94%

4-benzyloxy-3-nitrophenacyl bromide (43229-01-2) → (+/-)-2-bromo-1-(4-benzyloxy-3-nitrophenyl)ethanol (299964-35-5)

Conditions	Yield
With sodium tetrahydroborate In tetrahydrofuran at 0 - 20℃;	91%
With borane-THF In tetrahydrofuran at -20℃; Reduction;	87%
With sodium tetrahydroborate In methanol
With sodium tetrahydroborate In tetrahydrofuran

4-benzyloxy-3-nitrophenacyl bromide (43229-01-2) + 3,4-bis(3,4-dimethoxyphenyl)-1H-pyrrole-2,5-dione (653572-66-8) → 1-(2-(4-(benzyloxy)-3-nitrophenyl)-2-oxoethyl)-3,4-bis(3,4-dimethoxyphenyl)-1H-pyrrole-2,5-dione

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃;	74.1%

N-(tert-butoxycarbonyl)-4-aminobutanoic acid (57294-38-9) + 4-benzyloxy-3-nitrophenacyl bromide (43229-01-2) → 2-(4-(benzyloxy)-3-nitrophenyl)-2-oxoethyl-4-(tert-butoxycarbonylamino)butanoate (1292299-09-2)

Conditions	Yield
With potassium carbonate In acetonitrile at 20℃;	67%

2-Amino-4-methylpyridine (695-34-1) + 4-benzyloxy-3-nitrophenacyl bromide (43229-01-2) → 2-(4-benzyloxy-3-nitrophenyl)-7-methylimidazo<1,2-a>pyridine (141244-34-0)

Conditions	Yield
In acetonitrile for 7h; Heating;	65%

5-methylpyrazin-2-amine (5521-58-4) + 4-benzyloxy-3-nitrophenacyl bromide (43229-01-2) → 2-(4-(benzyloxy)-3-nitrophenyl)-6-methylimidazo[1,2-a]pyrazine (1254709-33-5)

Conditions	Yield
With sodium hydrogencarbonate In ethanol Reflux;	45%

4-benzyloxy-3-nitrophenacyl bromide (43229-01-2) → (S)-4-benzyloxy-3-nitrostyrene oxide (188730-96-3) + (S)-1-(4-(benzyloxy)-3-nitrophenyl)-2-bromoethanol (193761-53-4) + (R)-2-bromo-1-(4-benzyloxy-3-nitrophenyl)ethanol (188690-82-6)

Conditions	Yield
With sodium formate; Triton X-100; (R,R)-TsDPEN; dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer In water at 28℃; for 6h; Title compound not separated from byproducts;	A 7% B n/a C n/a

4-benzyloxy-3-nitrophenacyl bromide (43229-01-2) → 2-(3-benzyloxy-4-nitrophenyl)oxirane (51582-41-3)

Conditions	Yield
With sodium hydroxide; sodium tetrahydroborate 1.) MeOH; Multistep reaction;
With sodium tetrahydroborate In methanol at 20℃; for 3h;

4-benzyloxy-3-nitrophenacyl bromide (43229-01-2) + dibenzylamine (103-49-1) → ω-(dibenzylamino)-4-benzyloxy-3-nitroacetophenone (173283-38-0)

Conditions	Yield
In benzene for 72h; Ambient temperature;

4-benzyloxy-3-nitrophenacyl bromide (43229-01-2) → (S)-1-(4-(benzyloxy)-3-nitrophenyl)-2-bromoethanol (193761-53-4) + (R)-2-bromo-1-(4-benzyloxy-3-nitrophenyl)ethanol (188690-82-6)

Conditions	Yield
With boron trifluoride-tetrahydrofuran complex; (-)-(1R,2S)-1-amino-2-hydroxy-1,2,3,4-tetrahydronaphthalene In tetrahydrofuran at 0℃; for 2h; Product distribution; other reag., other temp.;
With borane N,N-diethylaniline complex; (S)-Corey-Bakshi-Shibata oxazaborolidine In 1,2-dimethoxyethane; dichloromethane; water at 25 - 30℃; for 9h; Corey-Itsuno reduction; Inert atmosphere; optical yield given as %ee;
With borane N,N-diethylaniline complex; (1R,2S)-1-Amino-2-indanol In tetrahydrofuran at 25℃; for 1h; Concentration; enantioselective reaction;	A n/a B n/a
With dimethylsulfide borane complex; C9H10BNO In tetrahydrofuran at 25℃; for 2h; Temperature; Inert atmosphere; Cooling with ice; enantioselective reaction;	A n/a B n/a

4-benzyloxy-3-nitrophenacyl bromide (43229-01-2) → 2-benzyloxy-5-vinylaniline (876753-52-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: NaBH4 / methanol / 3 h / 20 °C 2: HOAc / methanol 3: 10.6 g / triphenylphosphine; imidazole; iodine / toluene / 3 h / Heating 4: 79.5 percent / Fe; HOAc / methanol / 2 h / Heating View Scheme

4-benzyloxy-3-nitrophenacyl bromide (43229-01-2) → 2-benzyloxy-5-vinylnitrobenzene (515152-69-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: NaBH4 / methanol / 3 h / 20 °C 2: HOAc / methanol 3: 10.6 g / triphenylphosphine; imidazole; iodine / toluene / 3 h / Heating View Scheme

4-benzyloxy-3-nitrophenacyl bromide (43229-01-2) → N-(2-(benzyloxy)-5-(oxiran-2-yl)phenyl)formamide

Conditions	Yield
Multi-step reaction with 6 steps 1: NaBH4 / methanol / 3 h / 20 °C 2: HOAc / methanol 3: 10.6 g / triphenylphosphine; imidazole; iodine / toluene / 3 h / Heating 4: 79.5 percent / Fe; HOAc / methanol / 2 h / Heating 5: acetic anhydride / CH2Cl2 / 1.5 h / 0 °C 6: 1.15 g / m-CPBA; NaHCO3 / CH2Cl2; H2O / 3 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1: sodium tetrahydroborate / tetrahydrofuran 2: platinum on carbon; dimethylsulfide; hydrogen 3: acetic anhydride 4: potassium carbonate / tetrahydrofuran; methanol View Scheme
Multi-step reaction with 4 steps 1: sodium tetrahydroborate / tetrahydrofuran / 0 - 20 °C 2: hydrogen; platinum on carbon; dimethylsulfide 3: acetic anhydride / 0 - 20 °C 4: potassium carbonate / methanol; tetrahydrofuran View Scheme

4-benzyloxy-3-nitrophenacyl bromide (43229-01-2) → N-(2-benzyloxy-5-vinylphenyl)formamide (876753-53-6)

Conditions	Yield
Multi-step reaction with 5 steps 1: NaBH4 / methanol / 3 h / 20 °C 2: HOAc / methanol 3: 10.6 g / triphenylphosphine; imidazole; iodine / toluene / 3 h / Heating 4: 79.5 percent / Fe; HOAc / methanol / 2 h / Heating 5: acetic anhydride / CH2Cl2 / 1.5 h / 0 °C View Scheme

4-benzyloxy-3-nitrophenacyl bromide (43229-01-2) → (4-benzyloxy-3-nitrophenyl)ethane-1,2-diol (876753-51-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: NaBH4 / methanol / 3 h / 20 °C 2: HOAc / methanol View Scheme

4-benzyloxy-3-nitrophenacyl bromide (43229-01-2) → (R)-1-(4-benzyloxy-3-nitrophenyl)oxirane (188730-94-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 87 percent / BH3*THF / tetrahydrofuran / -20 °C 2: lipase PS Celite-immobilized / various solvent(s) / 72 h / 37 °C 3: K2CO3 / methanol / 2.5 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1.1: BH3*THF / tetrahydrofuran / -20 °C 1.2: 48 percent / lipase PS; vinyl acetate / various solvent(s) / 72 h / 37 °C 2.1: K2CO3 / methanol / 2.5 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: 98 percent / oxazaborolidine from cis (1R,2S)-aminoindanol and trimethylboroxine, BH3 / tetrahydrofuran / -15 °C 2: 98 percent / aqueous sodium hydroxide / methanol / 0.5 h View Scheme
Multi-step reaction with 2 steps 1: (-)-diisopinocamphenylborane chloride / dichloromethane / 20 - 30 °C / Inert atmosphere 2: potassium carbonate / tetrahydrofuran; methanol / 20 - 30 °C View Scheme

4-benzyloxy-3-nitrophenacyl bromide (43229-01-2) → (S)-4-benzyloxy-3-nitrostyrene oxide (188730-96-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 87 percent / BH3*THF / tetrahydrofuran / -20 °C 2: lipase PS Celite-immobilized / various solvent(s) / 72 h / 37 °C 3: K2CO3 / methanol / 2.5 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1.1: BH3*THF / tetrahydrofuran / -20 °C 1.2: 48 percent / lipase PS; vinyl acetate / various solvent(s) / 72 h / 37 °C 2.1: K2CO3 / methanol / 2.5 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: 98 percent / oxazaborolidine from cis (1S,2R)-aminoindanol and trimethylboroxine, BH3 / tetrahydrofuran / -15 °C 2: 98 percent / aqueous sodium hydroxide / methanol / 0.5 h View Scheme

4-benzyloxy-3-nitrophenacyl bromide (43229-01-2) → (R,R)-formoterol (73573-87-2)

Conditions	Yield
Multi-step reaction with 8 steps 1: 87 percent / BH3*THF / tetrahydrofuran / -20 °C 2: lipase PS Celite-immobilized / various solvent(s) / 72 h / 37 °C 3: K2CO3 / methanol / 2.5 h / 20 °C 4: dimethylsulfoxide / 87 h / 80 °C 5: neutral Al2O3 (activity III) 6: 67 percent / Fe turnings; 1M aq. HCl / methanol / 0.75 h / Heating 7: 69 percent / pyridine / 6.5 h / 60 °C 8: H2 / 10 percentPd/C / ethanol / 20 °C View Scheme
Multi-step reaction with 7 steps 1.1: BH3*THF / tetrahydrofuran / -20 °C 1.2: 48 percent / lipase PS; vinyl acetate / various solvent(s) / 72 h / 37 °C 2.1: K2CO3 / methanol / 2.5 h / 20 °C 3.1: dimethylsulfoxide / 87 h / 80 °C 4.1: neutral Al2O3 (activity III) 5.1: 67 percent / Fe turnings; 1M aq. HCl / methanol / 0.75 h / Heating 6.1: 69 percent / pyridine / 6.5 h / 60 °C 7.1: H2 / 10 percentPd/C / ethanol / 20 °C View Scheme
Multi-step reaction with 6 steps 1: 98 percent / oxazaborolidine from cis (1R,2S)-aminoindanol and trimethylboroxine, BH3 / tetrahydrofuran / -15 °C 2: 98 percent / aqueous sodium hydroxide / methanol / 0.5 h 3: 90 °C 4: H2 / PtO2 6: H2 / Pd-C / ethanol View Scheme

4-benzyloxy-3-nitrophenacyl bromide (43229-01-2) → Acetic acid (R)-1-(4-benzyloxy-3-nitro-phenyl)-2-bromo-ethyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: 87 percent / BH3*THF / tetrahydrofuran / -20 °C 2: lipase PS Celite-immobilized / various solvent(s) / 72 h / 37 °C View Scheme

4-benzyloxy-3-nitrophenacyl bromide (43229-01-2) → Acetic acid (S)-1-(4-benzyloxy-3-nitro-phenyl)-2-bromo-ethyl ester (299964-37-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 87 percent / BH3*THF / tetrahydrofuran / -20 °C 2: lipase PS Celite-immobilized / various solvent(s) / 72 h / 37 °C View Scheme

4-benzyloxy-3-nitrophenacyl bromide (43229-01-2) → (R)-1-(3-Amino-4-benzyloxy-phenyl)-2-[(R)-2-(4-methoxy-phenyl)-1-methyl-ethylamino]-ethanol (299964-43-5)

Conditions	Yield
Multi-step reaction with 6 steps 1: 87 percent / BH3*THF / tetrahydrofuran / -20 °C 2: lipase PS Celite-immobilized / various solvent(s) / 72 h / 37 °C 3: K2CO3 / methanol / 2.5 h / 20 °C 4: dimethylsulfoxide / 87 h / 80 °C 5: neutral Al2O3 (activity III) 6: 67 percent / Fe turnings; 1M aq. HCl / methanol / 0.75 h / Heating View Scheme
Multi-step reaction with 5 steps 1.1: BH3*THF / tetrahydrofuran / -20 °C 1.2: 48 percent / lipase PS; vinyl acetate / various solvent(s) / 72 h / 37 °C 2.1: K2CO3 / methanol / 2.5 h / 20 °C 3.1: dimethylsulfoxide / 87 h / 80 °C 4.1: neutral Al2O3 (activity III) 5.1: 67 percent / Fe turnings; 1M aq. HCl / methanol / 0.75 h / Heating View Scheme

4-benzyloxy-3-nitrophenacyl bromide (43229-01-2) → (R)-1-(4-Benzyloxy-3-nitro-phenyl)-2-[(R)-2-(4-methoxy-phenyl)-1-methyl-ethylamino]-ethanol (245759-61-9)

Conditions	Yield
Multi-step reaction with 5 steps 1: 87 percent / BH3*THF / tetrahydrofuran / -20 °C 2: lipase PS Celite-immobilized / various solvent(s) / 72 h / 37 °C 3: K2CO3 / methanol / 2.5 h / 20 °C 4: dimethylsulfoxide / 87 h / 80 °C 5: neutral Al2O3 (activity III) View Scheme
Multi-step reaction with 4 steps 1.1: BH3*THF / tetrahydrofuran / -20 °C 1.2: 48 percent / lipase PS; vinyl acetate / various solvent(s) / 72 h / 37 °C 2.1: K2CO3 / methanol / 2.5 h / 20 °C 3.1: dimethylsulfoxide / 87 h / 80 °C 4.1: neutral Al2O3 (activity III) View Scheme

4-benzyloxy-3-nitrophenacyl bromide (43229-01-2) → N-(2-Benzyloxy-5-{(R)-1-hydroxy-2-[(R)-2-(4-methoxy-phenyl)-1-methyl-ethylamino]-ethyl}-phenyl)-formamide (408497-91-6)

Conditions	Yield
Multi-step reaction with 7 steps 1: 87 percent / BH3*THF / tetrahydrofuran / -20 °C 2: lipase PS Celite-immobilized / various solvent(s) / 72 h / 37 °C 3: K2CO3 / methanol / 2.5 h / 20 °C 4: dimethylsulfoxide / 87 h / 80 °C 5: neutral Al2O3 (activity III) 6: 67 percent / Fe turnings; 1M aq. HCl / methanol / 0.75 h / Heating 7: 69 percent / pyridine / 6.5 h / 60 °C View Scheme
Multi-step reaction with 6 steps 1.1: BH3*THF / tetrahydrofuran / -20 °C 1.2: 48 percent / lipase PS; vinyl acetate / various solvent(s) / 72 h / 37 °C 2.1: K2CO3 / methanol / 2.5 h / 20 °C 3.1: dimethylsulfoxide / 87 h / 80 °C 4.1: neutral Al2O3 (activity III) 5.1: 67 percent / Fe turnings; 1M aq. HCl / methanol / 0.75 h / Heating 6.1: 69 percent / pyridine / 6.5 h / 60 °C View Scheme

4-benzyloxy-3-nitrophenacyl bromide (43229-01-2) → [(R)-2-(4-Benzyloxy-3-nitro-phenyl)-2-trimethylsilanyloxy-ethyl]-[(R)-2-(4-methoxy-phenyl)-1-methyl-ethyl]-amine

Conditions	Yield
Multi-step reaction with 4 steps 1: 87 percent / BH3*THF / tetrahydrofuran / -20 °C 2: lipase PS Celite-immobilized / various solvent(s) / 72 h / 37 °C 3: K2CO3 / methanol / 2.5 h / 20 °C 4: dimethylsulfoxide / 87 h / 80 °C View Scheme
Multi-step reaction with 3 steps 1.1: BH3*THF / tetrahydrofuran / -20 °C 1.2: 48 percent / lipase PS; vinyl acetate / various solvent(s) / 72 h / 37 °C 2.1: K2CO3 / methanol / 2.5 h / 20 °C 3.1: dimethylsulfoxide / 87 h / 80 °C View Scheme

4-benzyloxy-3-nitrophenacyl bromide (43229-01-2) → (S,R)-Formoterol (67346-50-3)

Conditions	Yield
Multi-step reaction with 6 steps 1: 98 percent / oxazaborolidine from cis (1S,2R)-aminoindanol and trimethylboroxine, BH3 / tetrahydrofuran / -15 °C 2: 98 percent / aqueous sodium hydroxide / methanol / 0.5 h 3: 90 °C 4: H2 / PtO2 6: H2 / Pd-C / ethanol View Scheme

4-benzyloxy-3-nitrophenacyl bromide (43229-01-2) → N-(2-Hydroxy-5-{(R)-1-hydroxy-2-[(S)-2-(4-methoxy-phenyl)-1-methyl-ethylamino]-ethyl}-phenyl)-formamide (67346-51-4)

Conditions	Yield
Multi-step reaction with 6 steps 1: 98 percent / oxazaborolidine from cis (1R,2S)-aminoindanol and trimethylboroxine, BH3 / tetrahydrofuran / -15 °C 2: 98 percent / aqueous sodium hydroxide / methanol / 0.5 h 3: 90 °C 4: H2 / PtO2 6: H2 / Pd-C / ethanol View Scheme

4-benzyloxy-3-nitrophenacyl bromide (43229-01-2) → (S,S)-formoterol

Conditions	Yield
Multi-step reaction with 6 steps 1: 98 percent / oxazaborolidine from cis (1S,2R)-aminoindanol and trimethylboroxine, BH3 / tetrahydrofuran / -15 °C 2: 98 percent / aqueous sodium hydroxide / methanol / 0.5 h 3: 90 °C 4: H2 / PtO2 6: H2 / Pd-C / ethanol View Scheme

Upstream product

• 6322-56-1 4'-hydroxy-3'-nitroacetophenone 
• 100-44-7 benzyl chloride 
• 100-39-0 benzyl bromide 
• 99-93-4 4-Hydroxyacetophenone 
• 14347-05-8 4-benzyloxy-3-nitroacetophenone 

Downstream Products

• 141244-34-0 2-(4-benzyloxy-3-nitrophenyl)-7-methylimidazo<1,2-a>pyridine 
• 51582-41-3 2-(3-benzyloxy-4-nitrophenyl)oxirane 
• 299964-35-5 (+/-)-2-bromo-1-(4-benzyloxy-3-nitrophenyl)ethanol 
• 193761-53-4 (S)-1-(4-(benzyloxy)-3-nitrophenyl)-2-bromoethanol 
• 188690-82-6 (R)-2-bromo-1-(4-benzyloxy-3-nitrophenyl)ethanol 
• 312753-82-5 2-[benzyl-(5,6-diethyl-indan-2-yl)-amino]-1-(4-benzyloxy-3-nitro-phenyl)-ethanone 
• 861448-71-7 N-[2-(benzyloxy)-5-((1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)phenyl]methane sulfonamide 
• 861448-79-5 (3-{2-[(2R)-2-(4-benzyloxy-3-methanesulfonylaminophenyl)-2-(tert-butyldimethylsilanyloxy)ethylamino]-2-methylpropyl}phenyl)acetic acid methyl ester 
• 861448-88-6 methyl (3-{2-[((2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-{4-hydroxy-3-[(methylsulfonyl)amino]phenyl}ethyl)amino]-2-methylpropyl}phenyl)acetate 
• 861448-89-7 (3-{2-[(2R)-2-(tert-butyldimethylsilyloxy)-2-(4-hydroxy-3-methanesulfonylaminophenyl)ethylamino]-2-methylpropyl}phenyl)acetic acid 
• 862540-80-5 2-[3-(2-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-{4-hydroxy-3-[(methylsulfonyl)amino]phenyl}ethyl]amino}-2-methylpropyl)phenyl]-N-[(4'-hydroxybiphenyl-3-yl)methyl]acetamide 
• 861448-91-1 ethyl (3-{2-[((2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-{4-benzyloxy-3-[(methylsulfonyl)amino]phenyl}ethyl)amino]-2-methylpropyl}phenyl)acetate 
• 861448-92-2 ethyl (R)-2-(3-{2-[2-hydroxy-2-(4-benzyloxy-3-methanesulfonamidophenyl)ethylamino]-2-methylpropyl}phenyl)acetate 
• 861448-93-3 [3-(2-{[(2R)-2-{4-(benzyloxy)-3-[(methylsulfonyl)amino]phenyl}-2-hydroxyethyl]amino}-2-methylpropyl)phenyl]acetic acid 

Relevant articles and documents

Preparation method of 3-nitro-4-benzyloxy-2-bromoacetophenone

The invention relates to a preparation method of 3-nitro-4-benzyloxy-2-bromoacetophenone. Particularly, 3-nitro-4-hydroxyacetophenone and benzyl bromide are taken as raw materials, and 3-nitro-4-benzyloxy-2-bromoacetophenone is synthesized through hydroxy protection and trimethylphenylammonium tribromide bromination reaction in a high-yield manner. The preparation method of 3-nitro-4-benzyloxy-2-bromoacetophenone in the synthesis route is high in yield, low in cost, easy to operate and suitable for industrialization.

Design, synthesis and evaluation of dual pharmacology β2- adrenoceptor agonists and PDE4 inhibitors

A novel series of formoterol-phthalazinone hybrids were synthesised and evaluated as dual pharmacology β2-adrenoceptor agonists and PDE4 inhibitors. Most of the hybrids displayed high β2-adrenoceptor agonist and moderate PDE4 inhibitory activities. The most potent compound, (R,R)-11c, exhibited agonist (EC50 = 1.05 nM, pEC50 = 9.0) and potent PDE4B2 inhibitory activities (IC50 = 0.092 μM).

Development of an enabling route to PF-00610355: A novel inhaled β2-adrenoreceptor agonist

The initial route used to prepare PF-00610355 (8) for early clinical development is described. Through careful choice of solvent, an efficient, telescoped route to carboxylic acid 23 was developed, affording this late-stage intermediate in 80% yield over 4 steps. Deprotection of 23 to give sodium salt 24a and coupling with amine 6·HCl afforded the desired API. Effective synthetic routes to two of the starting materials, chiral bromide 1 and amine 6, are also described.