172900-83-3

Basic information

• Product Name: Aliskiren inter-8
• Synonyms: Aliskiren inter-8;tert-Butyl [(1S,3S)-3-[3-(3-methoxypropoxy)-4-methoxybenzyl]-1-formyl-4-methylpentyl]carbamate;(1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester;CarbaMic acid,[3-[[4-(1,1-diMethylethyl)phenyl]Methyl]-1-forMyl-4-Methylpentyl]-,1,1-diMethylethyl ester, [S-(R*,R*)]-CarbaMic acid;tert-Butyl ((2S,4S)-4-(4-Methoxy-3-(3-Methoxypropoxy)benzyl)-5-Methyl-1-oxohexan-2-yl)carbaMate;Carbamic acid, [3-[[4-(1,1-dimethylethyl)phenyl]methyl]-1-formyl-4-methylpentyl]-, 1,1-dimethylethyl ester, [S-(R*,R*)]-;tert-Butyl ((2S,4S)-4-(4-methoxy-3-(3-methoxypropoxy)-benzyl)-5-methyl-1-oxohexan-2-yl)carbama;tert-butyl ((2S,4S)-4-(4-methoxy-3-(3-methoxypropoxy)benzyl)-5-methyl-1-oxohexan-2-yl)carbamate(WXG03361)
• CAS NO: 172900-83-3
• Molecular Formula: C₂₄H₃₉NO₆
• Molecular Weight: 437.57
• Mol File: 172900-83-3.mol
• Article Data: 5

Chemical Properties

• Boiling Point: 554.43 °C at 760 mmHg
• Flash Point: 289.109 °C
• Appearance: /
• Density: 1.045
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.491
• Storage Temp.: 2-8°C
• CAS DataBase Reference: Aliskiren inter-8(CAS DataBase Reference)
• NIST Chemistry Reference: Aliskiren inter-8(172900-83-3)
• EPA Substance Registry System: Aliskiren inter-8(172900-83-3)

Safety Data

• Hazardous Substances Data: 172900-83-3(Hazardous Substances Data)

Usage

Uses

liquid crystal intermediate

InChI:InChI=1/C24H39NO6/c1-17(2)19(15-20(16-26)25-23(27)31-24(3,4)5)13-18-9-10-21(29-7)22(14-18)30-12-8-11-28-6/h9-10,14,16-17,19-20H,8,11-13,15H2,1-7H3,(H,25,27)/t19-,20-/m0/s1

Synthetic route

(2S,4S)-2-{[(tert-butoxy)carbonyl]amino}-4-[4-methoxy-3-(3-methoxypropoxy)benzyl]-5-methylhexan-1-ol (172900-82-2) → (1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3)

Conditions	Yield
With sulfur trioxide pyridine complex; triethylamine In dimethyl sulfoxide at 0 - 20℃; for 1h;	100%
With sulfur trioxide pyridine complex; dimethyl sulfoxide; triethylamine at 0 - 20℃; for 1h;	100%
With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane Swern oxidation;	89%

methyl (2S,4S)-2-{[(tert-butoxy)carbonyl]amino}-4-[4-methoxy-3-(3-methoxypropoxy)benzyl]-5-methylhexanoate (656241-21-3) → (1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3)

Conditions	Yield
With diisobutylaluminium hydride In toluene at -75℃; for 0.833333h;
Multi-step reaction with 2 steps 1: lithium borohydride / tetrahydrofuran / 15 h / 20 °C 2: sulfur trioxide pyridine complex; dimethyl sulfoxide; triethylamine / 1 h / 0 - 20 °C View Scheme

(2R,5S)-3,6-diethoxy-2-isopropyl-5-((S)-2-(4-methoxy-3-(3-methoxypropoxy)benzyl)-3-methylbutyl)-2,5-dihydropyrazine (866030-33-3) → (1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: HCl / acetonitrile 2: Et3N 3: NaBH4 / ethanol 4: 89 percent / DMSO; ClC(O)C(O)Cl; Et3N / CH2Cl2 View Scheme

isovanillin (621-59-0) → (1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3)

Conditions	Yield
Multi-step reaction with 12 steps 1: 98 percent / K2CO3 / acetonitrile 2: NaBH4 / ethanol 3: PBr3 / CH2Cl2 4: 76 percent / LiHMDS / tetrahydrofuran 5: 81 percent / LiOH; H2O2 6: 95 percent / LAH / tetrahydrofuran 7: 97 percent / PPh3; NBS / CH2Cl2 8: 68 percent / n-BuLi 9: HCl / acetonitrile 10: Et3N 11: NaBH4 / ethanol 12: 89 percent / DMSO; ClC(O)C(O)Cl; Et3N / CH2Cl2 View Scheme
Multi-step reaction with 11 steps 1.1: di-isopropyl azodicarboxylate; triphenylphosphine / tetrahydrofuran; toluene / 24 h / 20 °C 2.1: sodium tetrahydroborate; ethanol / 20 °C 3.1: pyridine; phosphorus tribromide / diethyl ether / 3 h / 20 °C 4.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.5 h / Cooling with acetone-dry ice 4.2: 20 °C / Cooling with acetone-dry ice 5.1: lithium borohydride; water / diethyl ether / 0.67 h / 0 °C 6.1: 1H-imidazole; iodine; triphenylphosphine / dichloromethane / 3 h 7.1: n-butyllithium / tetrahydrofuran; hexane / 0.75 h / Cooling with acetone-dry ice 7.2: 16.17 h / -78 °C / Cooling with acetone-dry ice 8.1: hydrogenchloride; water / acetonitrile / 3 h / 20 °C 8.2: 0 °C 9.1: dichloromethane / 14 h / 20 °C 10.1: lithium borohydride / tetrahydrofuran / 15 h / 20 °C 11.1: sulfur trioxide pyridine complex; dimethyl sulfoxide; triethylamine / 1 h / 0 - 20 °C View Scheme

(R)-4-benzyl-3-(3-methylbutyryl)oxazolidin-2-one (145589-03-3) → (1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3)

Conditions	Yield
Multi-step reaction with 9 steps 1: 76 percent / LiHMDS / tetrahydrofuran 2: 81 percent / LiOH; H2O2 3: 95 percent / LAH / tetrahydrofuran 4: 97 percent / PPh3; NBS / CH2Cl2 5: 68 percent / n-BuLi 6: HCl / acetonitrile 7: Et3N 8: NaBH4 / ethanol 9: 89 percent / DMSO; ClC(O)C(O)Cl; Et3N / CH2Cl2 View Scheme
Multi-step reaction with 8 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.5 h / Cooling with acetone-dry ice 1.2: 20 °C / Cooling with acetone-dry ice 2.1: lithium borohydride; water / diethyl ether / 0.67 h / 0 °C 3.1: 1H-imidazole; iodine; triphenylphosphine / dichloromethane / 3 h 4.1: n-butyllithium / tetrahydrofuran; hexane / 0.75 h / Cooling with acetone-dry ice 4.2: 16.17 h / -78 °C / Cooling with acetone-dry ice 5.1: hydrogenchloride; water / acetonitrile / 3 h / 20 °C 5.2: 0 °C 6.1: dichloromethane / 14 h / 20 °C 7.1: lithium borohydride / tetrahydrofuran / 15 h / 20 °C 8.1: sulfur trioxide pyridine complex; dimethyl sulfoxide; triethylamine / 1 h / 0 - 20 °C View Scheme

4-methoxy-3-(3-methoxypropoxy)benzaldehyde (172900-75-3) → (1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3)

Conditions	Yield
Multi-step reaction with 11 steps 1: NaBH4 / ethanol 2: PBr3 / CH2Cl2 3: 76 percent / LiHMDS / tetrahydrofuran 4: 81 percent / LiOH; H2O2 5: 95 percent / LAH / tetrahydrofuran 6: 97 percent / PPh3; NBS / CH2Cl2 7: 68 percent / n-BuLi 8: HCl / acetonitrile 9: Et3N 10: NaBH4 / ethanol 11: 89 percent / DMSO; ClC(O)C(O)Cl; Et3N / CH2Cl2 View Scheme
Multi-step reaction with 10 steps 1.1: sodium tetrahydroborate; ethanol / 20 °C 2.1: pyridine; phosphorus tribromide / diethyl ether / 3 h / 20 °C 3.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.5 h / Cooling with acetone-dry ice 3.2: 20 °C / Cooling with acetone-dry ice 4.1: lithium borohydride; water / diethyl ether / 0.67 h / 0 °C 5.1: 1H-imidazole; iodine; triphenylphosphine / dichloromethane / 3 h 6.1: n-butyllithium / tetrahydrofuran; hexane / 0.75 h / Cooling with acetone-dry ice 6.2: 16.17 h / -78 °C / Cooling with acetone-dry ice 7.1: hydrogenchloride; water / acetonitrile / 3 h / 20 °C 7.2: 0 °C 8.1: dichloromethane / 14 h / 20 °C 9.1: lithium borohydride / tetrahydrofuran / 15 h / 20 °C 10.1: sulfur trioxide pyridine complex; dimethyl sulfoxide; triethylamine / 1 h / 0 - 20 °C View Scheme

(R)-2-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutanol (172900-70-8) → (1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3)

Conditions	Yield
Multi-step reaction with 6 steps 1: 97 percent / PPh3; NBS / CH2Cl2 2: 68 percent / n-BuLi 3: HCl / acetonitrile 4: Et3N 5: NaBH4 / ethanol 6: 89 percent / DMSO; ClC(O)C(O)Cl; Et3N / CH2Cl2 View Scheme
Multi-step reaction with 6 steps 1.1: 1H-imidazole; iodine; triphenylphosphine / dichloromethane / 3 h 2.1: n-butyllithium / tetrahydrofuran; hexane / 0.75 h / Cooling with acetone-dry ice 2.2: 16.17 h / -78 °C / Cooling with acetone-dry ice 3.1: hydrogenchloride; water / acetonitrile / 3 h / 20 °C 3.2: 0 °C 4.1: dichloromethane / 14 h / 20 °C 5.1: lithium borohydride / tetrahydrofuran / 15 h / 20 °C 6.1: sulfur trioxide pyridine complex; dimethyl sulfoxide; triethylamine / 1 h / 0 - 20 °C View Scheme

(R)-3-[4-methoxy-3-(3-methoxypropoxy)phenyl]-2-(1-methylethyl)propanoic acid (172900-71-9) → (1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3)

Conditions	Yield
Multi-step reaction with 7 steps 1: 95 percent / LAH / tetrahydrofuran 2: 97 percent / PPh3; NBS / CH2Cl2 3: 68 percent / n-BuLi 4: HCl / acetonitrile 5: Et3N 6: NaBH4 / ethanol 7: 89 percent / DMSO; ClC(O)C(O)Cl; Et3N / CH2Cl2 View Scheme

4-(bromomethyl)-1-methoxy-2-(3-methoxypropoxy)-benzene (172900-73-1) → (1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3)

Conditions	Yield
Multi-step reaction with 9 steps 1: 76 percent / LiHMDS / tetrahydrofuran 2: 81 percent / LiOH; H2O2 3: 95 percent / LAH / tetrahydrofuran 4: 97 percent / PPh3; NBS / CH2Cl2 5: 68 percent / n-BuLi 6: HCl / acetonitrile 7: Et3N 8: NaBH4 / ethanol 9: 89 percent / DMSO; ClC(O)C(O)Cl; Et3N / CH2Cl2 View Scheme
Multi-step reaction with 8 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.5 h / Cooling with acetone-dry ice 1.2: 20 °C / Cooling with acetone-dry ice 2.1: lithium borohydride; water / diethyl ether / 0.67 h / 0 °C 3.1: 1H-imidazole; iodine; triphenylphosphine / dichloromethane / 3 h 4.1: n-butyllithium / tetrahydrofuran; hexane / 0.75 h / Cooling with acetone-dry ice 4.2: 16.17 h / -78 °C / Cooling with acetone-dry ice 5.1: hydrogenchloride; water / acetonitrile / 3 h / 20 °C 5.2: 0 °C 6.1: dichloromethane / 14 h / 20 °C 7.1: lithium borohydride / tetrahydrofuran / 15 h / 20 °C 8.1: sulfur trioxide pyridine complex; dimethyl sulfoxide; triethylamine / 1 h / 0 - 20 °C View Scheme

[4-methoxy-3-(3-methoxypropoxy)-phenyl]methanol (172900-74-2) → (1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3)

Conditions	Yield
Multi-step reaction with 10 steps 1: PBr3 / CH2Cl2 2: 76 percent / LiHMDS / tetrahydrofuran 3: 81 percent / LiOH; H2O2 4: 95 percent / LAH / tetrahydrofuran 5: 97 percent / PPh3; NBS / CH2Cl2 6: 68 percent / n-BuLi 7: HCl / acetonitrile 8: Et3N 9: NaBH4 / ethanol 10: 89 percent / DMSO; ClC(O)C(O)Cl; Et3N / CH2Cl2 View Scheme
Multi-step reaction with 9 steps 1.1: pyridine; phosphorus tribromide / diethyl ether / 3 h / 20 °C 2.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.5 h / Cooling with acetone-dry ice 2.2: 20 °C / Cooling with acetone-dry ice 3.1: lithium borohydride; water / diethyl ether / 0.67 h / 0 °C 4.1: 1H-imidazole; iodine; triphenylphosphine / dichloromethane / 3 h 5.1: n-butyllithium / tetrahydrofuran; hexane / 0.75 h / Cooling with acetone-dry ice 5.2: 16.17 h / -78 °C / Cooling with acetone-dry ice 6.1: hydrogenchloride; water / acetonitrile / 3 h / 20 °C 6.2: 0 °C 7.1: dichloromethane / 14 h / 20 °C 8.1: lithium borohydride / tetrahydrofuran / 15 h / 20 °C 9.1: sulfur trioxide pyridine complex; dimethyl sulfoxide; triethylamine / 1 h / 0 - 20 °C View Scheme

(R)-4-(2-(bromomethyl)-3-methylbutyl)-1-methoxy-2-(3-methoxypropoxy)benzene (172900-69-5) → (1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: 68 percent / n-BuLi 2: HCl / acetonitrile 3: Et3N 4: NaBH4 / ethanol 5: 89 percent / DMSO; ClC(O)C(O)Cl; Et3N / CH2Cl2 View Scheme

(2S,4S)-2-Amino-4-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-5-methyl-hexanoic acid ethyl ester (172900-99-1) → (1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: Et3N 2: NaBH4 / ethanol 3: 89 percent / DMSO; ClC(O)C(O)Cl; Et3N / CH2Cl2 View Scheme

ethyl (2S,4S)-2-{[(tert-butoxy)carbonyl]amino}-4-[4-methoxy-3-(3-methoxypropoxy)benzyl]-5-methylhexanoate (172900-76-4) → (1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: NaBH4 / ethanol 2: 89 percent / DMSO; ClC(O)C(O)Cl; Et3N / CH2Cl2 View Scheme

(4R)-3-{(2R)-2-{[4-methoxy-3-(methoxypropoxy)phenyl]methyl-3-methyl}-1-oxobutyl}-4-(phenylmethyl)oxazolidin-2-one (172900-72-0) → (1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3)

Conditions	Yield
Multi-step reaction with 8 steps 1: 81 percent / LiOH; H2O2 2: 95 percent / LAH / tetrahydrofuran 3: 97 percent / PPh3; NBS / CH2Cl2 4: 68 percent / n-BuLi 5: HCl / acetonitrile 6: Et3N 7: NaBH4 / ethanol 8: 89 percent / DMSO; ClC(O)C(O)Cl; Et3N / CH2Cl2 View Scheme
Multi-step reaction with 7 steps 1.1: lithium borohydride; water / diethyl ether / 0.67 h / 0 °C 2.1: 1H-imidazole; iodine; triphenylphosphine / dichloromethane / 3 h 3.1: n-butyllithium / tetrahydrofuran; hexane / 0.75 h / Cooling with acetone-dry ice 3.2: 16.17 h / -78 °C / Cooling with acetone-dry ice 4.1: hydrogenchloride; water / acetonitrile / 3 h / 20 °C 4.2: 0 °C 5.1: dichloromethane / 14 h / 20 °C 6.1: lithium borohydride / tetrahydrofuran / 15 h / 20 °C 7.1: sulfur trioxide pyridine complex; dimethyl sulfoxide; triethylamine / 1 h / 0 - 20 °C View Scheme

(R)-­4-(2-(iodomethyl)­-3-­methylbutyl)-­1-­methoxy-2­-(3-­methoxypropoxy)benzene (900811-38-3) → (1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: n-butyllithium / tetrahydrofuran; hexane / 0.75 h / Cooling with acetone-dry ice 1.2: 16.17 h / -78 °C / Cooling with acetone-dry ice 2.1: hydrogenchloride; water / acetonitrile / 3 h / 20 °C 2.2: 0 °C 3.1: dichloromethane / 14 h / 20 °C 4.1: lithium borohydride / tetrahydrofuran / 15 h / 20 °C 5.1: sulfur trioxide pyridine complex; dimethyl sulfoxide; triethylamine / 1 h / 0 - 20 °C View Scheme

isopentanoyl chloride (108-12-3) → (1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3)

Conditions

Yield

Multi-step reaction with 9 steps 1.1: n-butyllithium / tetrahydrofuran; hexane / 0.5 h / Cooling with acetone-dry ice 1.2: 2.33 h / 0 °C / Cooling with acetone-dry ice 2.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.5 h / Cooling with acetone-dry ice 2.2: 20 °C / Cooling with acetone-dry ice 3.1: lithium borohydride; water / diethyl ether / 0.67 h / 0 °C 4.1: 1H-imidazole; iodine; triphenylphosphine / dichloromethane / 3 h 5.1: n-butyllithium / tetrahydrofuran; hexane / 0.75 h / Cooling with acetone-dry ice 5.2: 16.17 h / -78 °C / Cooling with acetone-dry ice 6.1: hydrogenchloride; water / acetonitrile / 3 h / 20 °C 6.2: 0 °C 7.1: dichloromethane / 14 h / 20 °C 8.1: lithium borohydride / tetrahydrofuran / 15 h / 20 °C 9.1: sulfur trioxide pyridine complex; dimethyl sulfoxide; triethylamine / 1 h / 0 - 20 °C View Scheme

methyl (2S,4S)-2-amino-4-[4-methoxy-3-(3-methoxypropoxy)benzyl]-5-methylhexanoate (656241-36-0) → (1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: dichloromethane / 14 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 15 h / 20 °C 3: sulfur trioxide pyridine complex; dimethyl sulfoxide; triethylamine / 1 h / 0 - 20 °C View Scheme

(2S,5R)-2,5-dihydro-3,6-dimethoxy-2-{(2S)-2-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-3-methylbutyl}-5-(1-methylethyl)pyrazine (656241-17-7) → (1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: hydrogenchloride; water / acetonitrile / 3 h / 20 °C 1.2: 0 °C 2.1: dichloromethane / 14 h / 20 °C 3.1: lithium borohydride / tetrahydrofuran / 15 h / 20 °C 4.1: sulfur trioxide pyridine complex; dimethyl sulfoxide; triethylamine / 1 h / 0 - 20 °C View Scheme

(1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3) + (2S)-(benzyloxymethyl)-3-methyl-butyl bromide (172901-00-7) → (1S,4S,2'S)-(4-benzyloxymethyl-2-hydroxy-1-{2'-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutyl}-5-methylhexyl)carbamic acid tert-butyl ester

Conditions	Yield
Stage #1: (2S)-(benzyloxymethyl)-3-methyl-butyl bromide With magnesium; ethylene dibromide In tetrahydrofuran at 55℃; for 0.333333h; Stage #2: (1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester In tetrahydrofuran at 20℃; for 3h; Further stages.;	53%
With magnesium
Stage #1: (2S)-(benzyloxymethyl)-3-methyl-butyl bromide With magnesium; ethylene dibromide In tetrahydrofuran at 55℃; for 0.833333h; Stage #2: (1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester In tetrahydrofuran at 5 - 20℃; for 3h;

(1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3) → tert-butyl (1S,3S)-3-(3-(3-methoxypropoxy)-4-methoxybenzyl)-4-methyl-1-((R)-oxiran-2-yl)pentylcarbamate (861901-07-7)

Conditions	Yield
Stage #1: trimethylsulfoxonium iodide With sodium hydride In dimethyl sulfoxide at 20℃; for 1h; Stage #2: (1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester In tetrahydrofuran; dimethyl sulfoxide at 20℃; for 1h;	46%

(1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3) + trimethylsulfoxonium iodide (1774-47-6) → tert-butyl (1S,3S)-3-(3-(3-methoxypropoxy)-4-methoxybenzyl)-4-methyl-1-((R)-oxiran-2-yl)pentylcarbamate (861901-07-7)

Conditions	Yield
Stage #1: trimethylsulfoxonium iodide With sodium hydride In dimethyl sulfoxide at 20℃; for 1h; Stage #2: (1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester In tetrahydrofuran; dimethyl sulfoxide at 20℃; for 1h; Product distribution / selectivity;	46%
Stage #1: trimethylsulfoxonium iodide With potassium tert-butylate at 20℃; Stage #2: (1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester In tetrahydrofuran; dimethyl sulfoxide at 0℃; for 2h;

(1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3) + methacrylic acid N-(butyl)amide (28384-61-4) → (1S,2S,2'S)-(4-butylcarbamoyl-2-hydroxy-1-{2'-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-3'-methyl-butyl}-pent-4-enyl)-carbamic acid tert-butyl ester + (1S,2R,2'S)-(4-butylcarbamoyl-2-hydroxy-1-{2'-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-3'-methyl-butyl}-pent-4-enyl)-carbamic acid tert-butyl ester

Conditions	Yield
Stage #1: methacrylic acid N-(butyl)amide With n-butyllithium In tetrahydrofuran; hexane at -78 - 0℃; for 0.5h; Stage #2: With triisopropoxytitanium(IV) chloride In tetrahydrofuran; hexane at -78℃; for 0.916667h; Stage #3: (1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester In tetrahydrofuran; hexane at -78℃; for 1.5h; Further stages.;	A 76 g B 188 g

(1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3) → tert-butyl (1S,3S)-1-((2R,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl)-3-(4-methoxy-3-(3-methoxypropoxy)benzyl)-4-methylpentylcarbamate

Conditions	Yield
Multi-step reaction with 3 steps 1: Mg 2: H2 / Pd(OH)2/C 3: TPAP; NMMO View Scheme

(1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3) → tert-butyl {(1S,3S)-1-((2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl)-3-[4-methoxy-3-(3-methoxypropoxy)benzyl]-4-methylpentyl}carbamate (866030-35-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: Mg 2: 23 percent / H2 / Pd(OH)2/C 3: 38 percent / TPAP; NMMO View Scheme

(1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3) → ((1S,2R,4S)-2-Hydroxy-4-hydroxymethyl-1-{(S)-2-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-3-methyl-butyl}-5-methyl-hexyl)-carbamic acid tert-butyl ester (866030-40-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: Mg 2: H2 / Pd(OH)2/C View Scheme

(1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3) → ((1S,2S,4S)-2-hydroxy-4-hydroxymethyl-1-((S)-2-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-3-methyl-butyl)-5-methyl-hexyl)-carbamic acid tert-butyl ester (866030-34-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: Mg 2: 23 percent / H2 / Pd(OH)2/C View Scheme

(1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3) → 4-epi-aliskiren

Conditions	Yield
Multi-step reaction with 5 steps 1: Mg 2: H2 / Pd(OH)2/C 3: TPAP; NMMO 4: 2-hydroxypyridine; Et3N 5: TMSCl; phenol / CH2Cl2 View Scheme

(1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3) → ((1S,2R,4S)-4-(2-Carbamoyl-2-methyl-propylcarbamoyl)-2-hydroxy-1-{(S)-2-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-3-methyl-butyl}-5-methyl-hexyl)-carbamic acid tert-butyl ester

Conditions	Yield
Multi-step reaction with 4 steps 1: Mg 2: H2 / Pd(OH)2/C 3: TPAP; NMMO 4: 2-hydroxypyridine; Et3N View Scheme

(1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3) → tert-butyl (3S,5S,6S,8S)-8-(3-amino-2,2-dimethyl-3-oxopropylcarbamoyl)-6-hydroxy-3-(4-methoxy-3-(3-methoxypropoxy)benzyl)-2,9-dimethyldecan-5-ylcarbamate (173338-07-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: Mg 2: 23 percent / H2 / Pd(OH)2/C 3: 38 percent / TPAP; NMMO 4: 65 percent / 2-hydroxypyridine; Et3N View Scheme

(1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3) → (2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide (173334-57-1)

Conditions	Yield
Multi-step reaction with 5 steps 1: Mg 2: 23 percent / H2 / Pd(OH)2/C 3: 38 percent / TPAP; NMMO 4: 65 percent / 2-hydroxypyridine; Et3N 5: TMSCl; phenol / CH2Cl2 View Scheme

(1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3) + propynoic acid ethyl ester (623-47-2) → (4S,5S,7S)-5-tert-Butoxycarbonylamino-4-hydroxy-7-[4-methoxy-3-(3-methoxypropoxy)benzyl]-8-methylnon-2-ynoic acid ethyl ester (878276-68-7)

Conditions	Yield
Stage #1: propynoic acid ethyl ester With lithium diisopropyl amide In tetrahydrofuran for 0.5h; Stage #2: (1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester In tetrahydrofuran at -78℃; for 1h;

(1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3) → tert-butyl {1(S)-(2-amino-1(S)-hydroxyethyl)-3(S)-[4-methoxy-3-(3-methoxypropoxy)benzyl]-4-methylpentyl}carbamate (861901-11-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hydride / dimethyl sulfoxide / 1 h / 20 °C 1.2: 1 h / 20 °C 2.1: ammonia; water / methanol / 20 °C View Scheme

(1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester (172900-83-3) → tert-butyl (2S,3S,5S)-5-(3-(3-methoxypropoxy)-4-methoxybenzyl)-1-(1,1-dioxo-4-methoxy-1,2,5-thiadiazol-3-ylamino)-2-hydroxy-6-methylheptan-3-ylcarbamate

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hydride / dimethyl sulfoxide / 1 h / 20 °C 1.2: 1 h / 20 °C 2.1: acetonitrile / 0.33 h / 90 °C / Microwave View Scheme

Upstream product

• 656241-17-7 (2S,5R)-2,5-dihydro-3,6-dimethoxy-2-{(2S)-2-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-3-methylbutyl}-5-(1-methylethyl)pyrazine 
• 656241-36-0 methyl (2S,4S)-2-amino-4-[4-methoxy-3-(3-methoxypropoxy)benzyl]-5-methylhexanoate 
• 108-12-3 isopentanoyl chloride 
• 900811-38-3 (R)--4-(2-(iodomethyl)--3--methylbutyl)--1--methoxy-2--(3--methoxypropoxy)benzene 
• 172900-72-0 (4R)-3-{(2R)-2-{[4-methoxy-3-(methoxypropoxy)phenyl]methyl-3-methyl}-1-oxobutyl}-4-(phenylmethyl)oxazolidin-2-one 
• 172900-76-4 ethyl (2S,4S)-2-{[(tert-butoxy)carbonyl]amino}-4-[4-methoxy-3-(3-methoxypropoxy)benzyl]-5-methylhexanoate 
• 172900-99-1 (2S,4S)-2-Amino-4-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-5-methyl-hexanoic acid ethyl ester 
• 172900-69-5 (R)-4-(2-(bromomethyl)-3-methylbutyl)-1-methoxy-2-(3-methoxypropoxy)benzene 
• 172900-74-2 [4-methoxy-3-(3-methoxypropoxy)-phenyl]methanol 
• 172900-73-1 4-(bromomethyl)-1-methoxy-2-(3-methoxypropoxy)-benzene 
• 172900-71-9 (R)-3-[4-methoxy-3-(3-methoxypropoxy)phenyl]-2-(1-methylethyl)propanoic acid 
• 172900-70-8 (R)-2-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutanol 
• 172900-75-3 4-methoxy-3-(3-methoxypropoxy)benzaldehyde 
• 145589-03-3 (R)-4-benzyl-3-(3-methylbutyryl)oxazolidin-2-one 

Downstream Products

• 172900-92-4 (1S,4S,2'S)-(4-benzyloxymethyl-2-hydroxy-1-{2'-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutyl}-5-methylhexyl)carbamic acid tert-butyl ester 
• 861901-11-3 tert-butyl {1(S)-(2-amino-1(S)-hydroxyethyl)-3(S)-[4-methoxy-3-(3-methoxypropoxy)benzyl]-4-methylpentyl}carbamate 
• 955021-64-4 3-((2S,3S,5S)-5-(3-(3-methoxypropoxy)-4-methoxybenzyl)-3-(tert-butoxycarbonylamino)-2-hydroxy-6-methylheptylamino)-4-hexylcyclobut-3-ene-1,2-dione 
• 955020-83-4 3-((2S,3S,5S)-5-(3-(3-methoxypropoxy)-4-methoxybenzyl)-3-(tert-butoxycarbonylamino)-2-hydroxy-6-methylheptylamino)-4-(benzylamino)cyclobut-3-ene-1,2-dione 
• 955021-57-5 3-((2S,3S,5S)-5-(3-(3-methoxypropoxy)-4-methoxybenzyl)-3-(tert-butoxycarbonylamino)-2-hydroxy-6-methylheptylamino)-4-(N-methyl-N-(2-methylpentan-2-yl)amino)cyclobut-3-ene-1,2-dione 
• 955021-69-9 tert-butyl (2S,3S,5S)-5-(3-(3-methoxypropoxy)-4-methoxybenzyl)-1-(1,1-dioxo-4-(phenethylamino)-1,2,5-thiadiazol-3-ylamino)-2-hydroxy-6-methylheptan-3-ylcarbamate 
• 878276-68-7 (4S,5S,7S)-5-tert-Butoxycarbonylamino-4-hydroxy-7-[4-methoxy-3-(3-methoxypropoxy)benzyl]-8-methylnon-2-ynoic acid ethyl ester 
• 861901-07-7 tert-butyl (1S,3S)-3-(3-(3-methoxypropoxy)-4-methoxybenzyl)-4-methyl-1-((R)-oxiran-2-yl)pentylcarbamate 
• 173334-57-1 (2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide 
• 173338-07-3 tert-butyl (3S,5S,6S,8S)-8-(3-amino-2,2-dimethyl-3-oxopropylcarbamoyl)-6-hydroxy-3-(4-methoxy-3-(3-methoxypropoxy)benzyl)-2,9-dimethyldecan-5-ylcarbamate 
• 866030-34-4 ((1S,2S,4S)-2-hydroxy-4-hydroxymethyl-1-((S)-2-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-3-methyl-butyl)-5-methyl-hexyl)-carbamic acid tert-butyl ester 
• 866030-40-2 ((1S,2R,4S)-2-Hydroxy-4-hydroxymethyl-1-{(S)-2-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-3-methyl-butyl}-5-methyl-hexyl)-carbamic acid tert-butyl ester 
• 866030-35-5 tert-butyl {(1S,3S)-1-((2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl)-3-[4-methoxy-3-(3-methoxypropoxy)benzyl]-4-methylpentyl}carbamate 

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