(E)-3-[(1R,2R,3S)-2-((R)-Cyano-methyl-methyl)-3-methyl-cyclohexyl]-2-((2S,3S,6R)-6-{(E)-3-[(2S,5S)-5-((R)-1-methoxy-ethyl)-tetrahydro-furan-2-yl]-propenyl}-3-methyl-tetrahydro-pyran-2-yl)-acrylic acid methyl ester

Base Information

• Chemical Name: (E)-3-[(1R,2R,3S)-2-((R)-Cyano-methyl-methyl)-3-methyl-cyclohexyl]-2-((2S,3S,6R)-6-{(E)-3-[(2S,5S)-5-((R)-1-methoxy-ethyl)-tetrahydro-furan-2-yl]-propenyl}-3-methyl-tetrahydro-pyran-2-yl)-acrylic acid methyl ester
• CAS No.: 142459-45-8
• Molecular Formula: C₃₀H₄₇NO₅
• Molecular Weight: 501.707
• Mol file: 142459-45-8.mol

Synonyms:

Chemical Property of (E)-3-[(1R,2R,3S)-2-((R)-Cyano-methyl-methyl)-3-methyl-cyclohexyl]-2-((2S,3S,6R)-6-{(E)-3-[(2S,5S)-5-((R)-1-methoxy-ethyl)-tetrahydro-furan-2-yl]-propenyl}-3-methyl-tetrahydro-pyran-2-yl)-acrylic acid methyl ester

Chemical Property:

Purity/Quality:

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

Useful:

Technology Process of (E)-3-[(1R,2R,3S)-2-((R)-Cyano-methyl-methyl)-3-methyl-cyclohexyl]-2-((2S,3S,6R)-6-{(E)-3-[(2S,5S)-5-((R)-1-methoxy-ethyl)-tetrahydro-furan-2-yl]-propenyl}-3-methyl-tetrahydro-pyran-2-yl)-acrylic acid methyl ester

There total 55 articles about (E)-3-[(1R,2R,3S)-2-((R)-Cyano-methyl-methyl)-3-methyl-cyclohexyl]-2-((2S,3S,6R)-6-{(E)-3-[(2S,5S)-5-((R)-1-methoxy-ethyl)-tetrahydro-furan-2-yl]-propenyl}-3-methyl-tetrahydro-pyran-2-yl)-acrylic acid methyl ester which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield:

(E)-(4R,5S)-4-Acetoxy-5-(methanesulfonyloxy)-2-hexenal (142459-13-0) → (E)-3-[(1R,2R,3S)-2-((R)-Cyano-methyl-methyl)-3-methyl-cyclohexyl]-2-((2S,3S,6R)-6-{(E)-3-[(2S,5S)-5-((R)-1-methoxy-ethyl)-tetrahydro-furan-2-yl]-propenyl}-3-methyl-tetrahydro-pyran-2-yl)-acrylic acid methyl ester (142459-45-8)

Guidance literature:

Multi-step reaction with 13 steps

1: 98 percent / H₂ / 10percent Pd/C / ethyl acetate / 4 h

2: methanol / 9.5 h / 5 °C

3: imidazole / dimethylformamide / 1 h / Ambient temperature

4: 93 percent / BF₃*OEt₂ / CH₂Cl₂ / 1 h / 0 °C

5: 83 percent / Bu₄NF / tetrahydrofuran

6: 1) NaH / 1) THF 2) r.t., 1 h

7: 99 percent / DIBALH / hexane; diethyl ether / 0.08 h

8: 1) oxalyl chloride, DMSO, 2) Et₃N / 1) CH₂Cl₂, -80 deg C - 60 deg C, 1 h, 2) - 40 deg C, 30 min

9: NaClO₂, 2-methyl-2-butene, NaH₂PO₄*2H₂O / 2-methyl-propan-2-ol / 0.33 h / Ambient temperature

10: 142 mg / diethyl ether

11: 1.23 g / LDA / tetrahydrofuran; hexane / 0.58 h / -100 °C

12: 1.17 g / DMAP, pyridine / 48 h / Ambient temperature

13: 1,8-diazabicyclo<5.4.0>undec-7-ene / 48 h / Ambient temperature

With pyridine; 1H-imidazole; dmap; sodium chlorite; sodium dihydrogenphosphate; 2-methyl-but-2-ene; oxalyl dichloride; boron trifluoride diethyl etherate; tetrabutyl ammonium fluoride; hydrogen; sodium hydride; diisobutylaluminium hydride; dimethyl sulfoxide; 1,8-diazabicyclo[5.4.0]undec-7-ene; triethylamine; lithium diisopropyl amide; palladium on activated charcoal; In tetrahydrofuran; methanol; diethyl ether; hexane; dichloromethane; ethyl acetate; N,N-dimethyl-formamide; tert-butyl alcohol;

DOI:10.1021/jo00036a026

Reference yield:

3-Methoxy-5-methyl-cyclohexa-2,5-dienecarboxylic acid (124908-71-0) → (E)-3-[(1R,2R,3S)-2-((R)-Cyano-methyl-methyl)-3-methyl-cyclohexyl]-2-((2S,3S,6R)-6-{(E)-3-[(2S,5S)-5-((R)-1-methoxy-ethyl)-tetrahydro-furan-2-yl]-propenyl}-3-methyl-tetrahydro-pyran-2-yl)-acrylic acid methyl ester (142459-45-8)

Guidance literature:

Multi-step reaction with 17 steps

1: diethyl ether

2: 8.28 g / DIBALH / hexane; diethyl ether / 1.5 h / -50 °C

3: 12.4 g / imidazole / CH₂Cl₂ / 0.25 h

4: 1) 2,6-di-tert-butylcresol, dichloromaleic anhydride 2) NaOMe / 1) chlorobenzene, 150 deg C, 24 h 2) MeOH, 0 deg C, 50 min

5: HF / acetonitrile / 1 h / 0 °C / Resolution: 1) isooctane, benzene, (Ac)2O, Amano lipase CES on Celite, 23 deg C, 5 h, 2) chromatography (silica gel, AcOEt/hexane), 3) recrystallization (Et₂O)

6: 99 percent / imidazole / CH₂Cl₂ / 1 h / Ambient temperature

7: 69 percent / 1) lithium hexamethyldisilazane, 2) HMPA / 1) THF, hexane, -50 deg C - -60 deg C, 1 h, 2) -35 deg C, 24 h

8: 98 percent / NH₂OH*HCl, pyridine / CH₂Cl₂ / 15 h / Heating

9: 1) TsCl, DMAP, pyridine, 2) LiCl, MeOH / 1) CH₂Cl₂, -80 deg C - r.t., 1 h, 2) r.t., 2 weeks

10: 72 percent / H₂ / 10percent Pd/C / ethanol

11: ethanol / 1.5 h / Heating

12: 627 mg / catecholborane, NaOAc*3H₂O / CHCl₃; tetrahydrofuran / 48 h / Heating

13: 473 mg / 5percent HF / acetonitrile / 0.75 h / 0 °C

14: 1) oxalyl chloride, DMSO, 2) Et₃N / 1) CH₂Cl₂, -80 deg C - -60 deg C, 1 h, 2) -60 deg C, 50 min

15: 1.23 g / LDA / tetrahydrofuran; hexane / 0.58 h / -100 °C

16: 1.17 g / DMAP, pyridine / 48 h / Ambient temperature

17: 1,8-diazabicyclo<5.4.0>undec-7-ene / 48 h / Ambient temperature

With pyridine; 1H-imidazole; methanol; N,N,N,N,N,N-hexamethylphosphoric triamide; dmap; dichloromaleic acid anhydride; oxalyl dichloride; 2,4-di-t-butyl-3-methyl phenol; hydrogen fluoride; hydroxylamine hydrochloride; hydrogen; sodium methylate; sodium acetate; diisobutylaluminium hydride; dimethyl sulfoxide; 1,8-diazabicyclo[5.4.0]undec-7-ene; triethylamine; p-toluenesulfonyl chloride; lithium chloride; lithium hexamethyldisilazane; lithium diisopropyl amide; benzo[1,3,2]dioxaborole; palladium on activated charcoal; In tetrahydrofuran; diethyl ether; ethanol; hexane; dichloromethane; chloroform; acetonitrile;

DOI:10.1021/jo00036a026

Reference yield:

3-Methoxy-5-methyl-cyclohexa-2,5-dienecarboxylic acid methyl ester → (E)-3-[(1R,2R,3S)-2-((R)-Cyano-methyl-methyl)-3-methyl-cyclohexyl]-2-((2S,3S,6R)-6-{(E)-3-[(2S,5S)-5-((R)-1-methoxy-ethyl)-tetrahydro-furan-2-yl]-propenyl}-3-methyl-tetrahydro-pyran-2-yl)-acrylic acid methyl ester (142459-45-8)

Guidance literature:

Multi-step reaction with 16 steps

1: 8.28 g / DIBALH / hexane; diethyl ether / 1.5 h / -50 °C

2: 12.4 g / imidazole / CH₂Cl₂ / 0.25 h

3: 1) 2,6-di-tert-butylcresol, dichloromaleic anhydride 2) NaOMe / 1) chlorobenzene, 150 deg C, 24 h 2) MeOH, 0 deg C, 50 min

4: HF / acetonitrile / 1 h / 0 °C / Resolution: 1) isooctane, benzene, (Ac)2O, Amano lipase CES on Celite, 23 deg C, 5 h, 2) chromatography (silica gel, AcOEt/hexane), 3) recrystallization (Et₂O)

5: 99 percent / imidazole / CH₂Cl₂ / 1 h / Ambient temperature

6: 69 percent / 1) lithium hexamethyldisilazane, 2) HMPA / 1) THF, hexane, -50 deg C - -60 deg C, 1 h, 2) -35 deg C, 24 h

7: 98 percent / NH₂OH*HCl, pyridine / CH₂Cl₂ / 15 h / Heating

8: 1) TsCl, DMAP, pyridine, 2) LiCl, MeOH / 1) CH₂Cl₂, -80 deg C - r.t., 1 h, 2) r.t., 2 weeks

9: 72 percent / H₂ / 10percent Pd/C / ethanol

10: ethanol / 1.5 h / Heating

11: 627 mg / catecholborane, NaOAc*3H₂O / CHCl₃; tetrahydrofuran / 48 h / Heating

12: 473 mg / 5percent HF / acetonitrile / 0.75 h / 0 °C

13: 1) oxalyl chloride, DMSO, 2) Et₃N / 1) CH₂Cl₂, -80 deg C - -60 deg C, 1 h, 2) -60 deg C, 50 min

14: 1.23 g / LDA / tetrahydrofuran; hexane / 0.58 h / -100 °C

15: 1.17 g / DMAP, pyridine / 48 h / Ambient temperature

16: 1,8-diazabicyclo<5.4.0>undec-7-ene / 48 h / Ambient temperature

With pyridine; 1H-imidazole; methanol; N,N,N,N,N,N-hexamethylphosphoric triamide; dmap; dichloromaleic acid anhydride; oxalyl dichloride; 2,4-di-t-butyl-3-methyl phenol; hydrogen fluoride; hydroxylamine hydrochloride; hydrogen; sodium methylate; sodium acetate; diisobutylaluminium hydride; dimethyl sulfoxide; 1,8-diazabicyclo[5.4.0]undec-7-ene; triethylamine; p-toluenesulfonyl chloride; lithium chloride; lithium hexamethyldisilazane; lithium diisopropyl amide; benzo[1,3,2]dioxaborole; palladium on activated charcoal; In tetrahydrofuran; diethyl ether; ethanol; hexane; dichloromethane; chloroform; acetonitrile;

DOI:10.1021/jo00036a026

upstream raw materials:

(R)-1-((S)-5-Methoxy-tetrahydro-furan-2-yl)-ethanol

(R)-6-Hydroxymethyl-3-methyl-tetrahydro-pyran-2-one

(R)-4-(2,2-dimethyl-1,3-dioxolan-4-yl)butyric acid

(R)-2,2-Dimethyl-1,3-dioxolane-4-butanoic acid, methyl ester

Downstream raw materials:

C₄₁H₆₈O₈Si

(Z)-3-[(1R,2R,3S)-2-((R)-Cyano-methyl-methyl)-3-methyl-cyclohexyl]-2-((2S,3S,6R)-6-{(E)-3-[(2S,5S)-5-((R)-1-methoxy-ethyl)-tetrahydro-furan-2-yl]-propenyl}-3-methyl-tetrahydro-pyran-2-yl)-acrylic acid methyl ester