124655-09-0

Basic information

• Product Name: (4R-Cis)-6-Hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetic acid 1,1-dimethylethyl ester
• Synonyms: D-6 (4R-Cis)-6-HydroxyMethyl-2,2-DiMethyl-1,3-Dioxane-4-AceticAcid,1,1-DiMethylthylEster;tert-Butyl (4R,6S)-6-(Hydroxymethyl)-2,2-dimethyl-1,3-dioxane-4-acetate;rosuvastatin intermediatesC-5;T-BUTYL-(3R,5S)-6-HYDROXY 3,5-O-ISOPROPYLIDENE 3,5-DIHYDROXYHEXANOATE;TERT-BUTYL [(4R,6S)-6-(HYDROXYMETHYL)-2,2-DIMETHYL-1,3-DIOXANE-4-YL] ACETATE;TERT-BUTYL (3R,5S)-6-HYDROXY 3,5-O-ISOPROPYLIDENE-3,5-DIHYDROXYHEXANOATE;2-[(4r,6s)-6-(hydroxymethyl)-2,2-dimethyl-1,3-dioxan-4-yl]acetic acid tert-butyl ester;(6S-Hydroxymethyl-2,2-dimethyl-[1,3]dioxan-4R-yl)acetic acid tert-butyl ester
• CAS NO: 124655-09-0
• Molecular Formula: C₁₃H₂₄O₅
• Molecular Weight: 260.33
• EINECS: 432-960-5
• Product Categories: chiral;Chiral Reagents;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 124655-09-0.mol
• Article Data: 26

Chemical Properties

• Boiling Point: 331°C
• Flash Point: 113°C
• Appearance: Colorless to light yellow liquid
• Density: 1.030
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.4500-1.4540
• Storage Temp.: -20°C Freezer
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 14.25±0.10(Predicted)
• CAS DataBase Reference: (4R-Cis)-6-Hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetic acid 1,1-dimethylethyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: (4R-Cis)-6-Hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetic acid 1,1-dimethylethyl ester(124655-09-0)
• EPA Substance Registry System: (4R-Cis)-6-Hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetic acid 1,1-dimethylethyl ester(124655-09-0)

Safety Data

• Hazardous Substances Data: 124655-09-0(Hazardous Substances Data)

Usage

Chemical Properties

Colorless to light yellow liqui

Uses

Different sources of media describe the Uses of 124655-09-0 differently. You can refer to the following data:
1. (4R-Cis)-6-Hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetic acid 1,1-dimethylethyl ester is a useful synthetic intermediate.
2. A useful synthetic intermediate in the preparation of Rosuvastatin (R700500) and its derivatives

InChI:InChI=1/C13H24O5/c1-12(2,3)18-11(15)7-9-6-10(8-14)17-13(4,5)16-9/h9-10,14H,6-8H2,1-5H3/t9-,10+/m1/s1

Synthetic route

tert-butyl 2-((4R,6S)-6-((benzyloxy)methyl)-2,2-dimethyl-1,3-dioxane-4-yl)acetate (151140-38-4) → 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0)

Conditions	Yield
With hydrogen; palladium on activated charcoal In ethyl acetate at 31 - 33℃; under 7600 Torr; for 5h;	100%
With palladium 10% on activated carbon; hydrogen In ethanol at 20℃; under 750.075 - 1500.15 Torr; Autoclave;	94%
With palladium 10% on activated carbon; hydrogen In ethyl acetate at 20℃; for 5h; Concentration;	94%
With H2; palladium-carbon In ethyl acetate
With palladium 10% on activated carbon; hydrogen In ethyl acetate at 25 - 30℃; under 7500.75 Torr; for 5h; Autoclave;

(4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6) → 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0)

Conditions	Yield
With potassium carbonate In methanol; water	98%
With methanol; potassium carbonate for 0.5h;	98%
With methanol; potassium carbonate at 20℃;	92%

tert-butyl (3R,5S)-6-(4-methylbenzyloxy)-3,5-O-isopropylidene-3,5-dihydroxyhexanoate → 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0)

Conditions	Yield
With hydrogen; palladium on activated charcoal In ethyl acetate at 32℃; under 15201 Torr; for 16h;	90%

tert-butyl 2-[(4R,6S)-6-formyl-2,2-dimethyl-1,3-dioxan-4-yl]acetate (124752-23-4) → 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0)

Conditions	Yield
With sodium tetrahydroborate In methanol at 0℃; for 2h;	83%
With sodium tetrahydroborate In methanol at 0℃;

C18H32O6 (1067638-10-1) → 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0)

Conditions	Yield
With sodium ethanolate In ethanol at 20℃; for 15h;	81%

tert-butyl 2-((4R,6S)-6-((tert-butyldiphenylsilyloxy)methyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate (124655-08-9) → 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0)

Conditions	Yield
With tetrabutyl ammonium fluoride In tetrahydrofuran at 0℃; for 3h;	80%

tert-butyl 2-((4R, 6S)-2,2-dimethyl-6-((E)-styryl)-1,3-dioxan-4-yl)acetate (143840-61-3) → 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0)

Conditions	Yield
With sodium tetrahydroborate; ozone 1.) methanol; Yield given. Multistep reaction;

→ 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / sodium metaperiodate, water / diethyl ether / 3 h / Ambient temperature 2: 83 percent / sodium borohydride / methanol / 2 h / 0 °C View Scheme
Multi-step reaction with 2 steps 1: 85 percent / NaIO4 / diethyl ether; H2O / 2 h / Ambient temperature 2: NaBH4 / methanol / 0 °C View Scheme

isopropyl (2S,3R,4S,6R)-7-t-butoxycarbonyl-2,3-bis(t-butyldimethylsilyloxy)-4,6-dihydroxyheptanoate (147489-00-7) → 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: 99 percent / p-toluenesulfonic acid / 2 h / Ambient temperature 2: 99 percent / tetrabutylammonium fluoride / tetrahydrofuran / 3 h / Ambient temperature 3: 85 percent / sodium metaperiodate, water / diethyl ether / 3 h / Ambient temperature 4: 83 percent / sodium borohydride / methanol / 2 h / 0 °C View Scheme
Multi-step reaction with 4 steps 1: 98 percent / p-TsOH / 2 h / Ambient temperature 2: 99 percent / (n-Bu)4NF / tetrahydrofuran / 3 h / Ambient temperature 3: 85 percent / NaIO4 / diethyl ether; H2O / 2 h / Ambient temperature 4: NaBH4 / methanol / 0 °C View Scheme

isopropyl (2S,3R,4S,6R)-7-t-butpxycarbonyl-2,3-bis(t-butyldimethylsilyloxy)-4,6-isopropylidenedioxyheptanoate (147489-01-8) → 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 99 percent / tetrabutylammonium fluoride / tetrahydrofuran / 3 h / Ambient temperature 2: 85 percent / sodium metaperiodate, water / diethyl ether / 3 h / Ambient temperature 3: 83 percent / sodium borohydride / methanol / 2 h / 0 °C View Scheme
Multi-step reaction with 3 steps 1: 99 percent / (n-Bu)4NF / tetrahydrofuran / 3 h / Ambient temperature 2: 85 percent / NaIO4 / diethyl ether; H2O / 2 h / Ambient temperature 3: NaBH4 / methanol / 0 °C View Scheme

isopropyl (2S,3S,6R)-7-t-butoxycarbonyl-2,3-bis(t-butyldimethylsilyloxy)-6-hydroxy-4-oxoheptanoate (147488-99-1) → 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0)

Conditions	Yield
Multi-step reaction with 5 steps 1: 1.) diethyl(methoxy)borane, 2.) sodium borohydride / 1.) THF, methanol, RT, 15 min, 2.) THF, methanol, a) -78 deg C, 4 h, b) from -78 deg C to RT, 8 h 2: 99 percent / p-toluenesulfonic acid / 2 h / Ambient temperature 3: 99 percent / tetrabutylammonium fluoride / tetrahydrofuran / 3 h / Ambient temperature 4: 85 percent / sodium metaperiodate, water / diethyl ether / 3 h / Ambient temperature 5: 83 percent / sodium borohydride / methanol / 2 h / 0 °C View Scheme
Multi-step reaction with 5 steps 1: 76 percent / Et2BOMe, NaBH4 / tetrahydrofuran; methanol / -78 deg C to RT, 12 h 2: 98 percent / p-TsOH / 2 h / Ambient temperature 3: 99 percent / (n-Bu)4NF / tetrahydrofuran / 3 h / Ambient temperature 4: 85 percent / NaIO4 / diethyl ether; H2O / 2 h / Ambient temperature 5: NaBH4 / methanol / 0 °C View Scheme

isopropyl (2S,3S)-7-t-butoxycarbonyl-2,3-bis(t-butyldimethylsilyloxy)-4,6-dioxoheptanoate (147488-98-0) → 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0)

Conditions	Yield
Multi-step reaction with 6 steps 1: 60 percent / DIBAL / tetrahydrofuran; hexane / 4 h / -78 °C 2: 1.) diethyl(methoxy)borane, 2.) sodium borohydride / 1.) THF, methanol, RT, 15 min, 2.) THF, methanol, a) -78 deg C, 4 h, b) from -78 deg C to RT, 8 h 3: 99 percent / p-toluenesulfonic acid / 2 h / Ambient temperature 4: 99 percent / tetrabutylammonium fluoride / tetrahydrofuran / 3 h / Ambient temperature 5: 85 percent / sodium metaperiodate, water / diethyl ether / 3 h / Ambient temperature 6: 83 percent / sodium borohydride / methanol / 2 h / 0 °C View Scheme
Multi-step reaction with 6 steps 1: 60 percent / diisobutylaluminium hydride / tetrahydrofuran; hexane / 4 h / -78 °C 2: 76 percent / Et2BOMe, NaBH4 / tetrahydrofuran; methanol / -78 deg C to RT, 12 h 3: 98 percent / p-TsOH / 2 h / Ambient temperature 4: 99 percent / (n-Bu)4NF / tetrahydrofuran / 3 h / Ambient temperature 5: 85 percent / NaIO4 / diethyl ether; H2O / 2 h / Ambient temperature 6: NaBH4 / methanol / 0 °C View Scheme

tert-butyl acetoacetate (1694-31-1) → 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0)

Conditions

Yield

Multi-step reaction with 7 steps 1: 74 percent / NaH, n-BuLi / 20 h / -78 °C 2: 60 percent / diisobutylaluminium hydride / tetrahydrofuran; hexane / 4 h / -78 °C 3: 76 percent / Et2BOMe, NaBH4 / tetrahydrofuran; methanol / -78 deg C to RT, 12 h 4: 98 percent / p-TsOH / 2 h / Ambient temperature 5: 99 percent / (n-Bu)4NF / tetrahydrofuran / 3 h / Ambient temperature 6: 85 percent / NaIO4 / diethyl ether; H2O / 2 h / Ambient temperature 7: NaBH4 / methanol / 0 °C View Scheme

(3R,5S)-3,5-Dihydroxy-5-((2S,3S)-3-trimethylsilanyl-oxiranyl)-pentanoic acid tert-butyl ester (143827-05-8) → 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 81 percent / H(1+) 2: 1.) Bu3SnLi / 2.) Pd(PPh3)4 3: 1.) O3, 2.) NaBH4 / 1.) methanol View Scheme
Multi-step reaction with 3 steps 1: 81 percent / H(1+) 2: 90 percent 3: 1.) O3, 2.) NaBH4 / 1.) methanol View Scheme

(S)-5-Hydroxy-3-oxo-5-((2S,3S)-3-trimethylsilanyl-oxiranyl)-pentanoic acid tert-butyl ester (143840-67-9) → 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: 60 percent / Et2BOMe, NaBH4 2: 81 percent / H(1+) 3: 1.) Bu3SnLi / 2.) Pd(PPh3)4 4: 1.) O3, 2.) NaBH4 / 1.) methanol View Scheme
Multi-step reaction with 4 steps 1: 60 percent / Et2BOMe, NaBH4 2: 81 percent / H(1+) 3: 90 percent 4: 1.) O3, 2.) NaBH4 / 1.) methanol View Scheme

[(4R,6S)-2,2-Dimethyl-6-((2S,3S)-3-trimethylsilanyl-oxiranyl)-[1,3]dioxan-4-yl]-acetic acid tert-butyl ester (143800-10-6) → 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) Bu3SnLi / 2.) Pd(PPh3)4 2: 1.) O3, 2.) NaBH4 / 1.) methanol View Scheme
Multi-step reaction with 2 steps 1: 90 percent 2: 1.) O3, 2.) NaBH4 / 1.) methanol View Scheme

acetic acid tert-butyl ester (540-88-5) → 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: 100 percent / LDA / tetrahydrofuran / 1.75 h / -70 - -15 °C 2: 1). Et3B; 2.) NaBH4, MeOH / 1.) THF, 23 deg C, 15 min; 2.) -70 deg C 3: 70 percent / p-toluenesulfonic acid / acetone / 2 h / 23 °C 4: 80 percent / Bu4NF / tetrahydrofuran / 3 h / 0 °C View Scheme
Multi-step reaction with 5 steps 1.1: lithium diisopropyl amide / tetrahydrofuran / 2 h / 0 °C / Inert atmosphere 1.2: 2 h / 20 °C / Inert atmosphere 2.1: sodium hydride / N,N-dimethyl-formamide / 2 h / 20 °C / Inert atmosphere 2.2: 6 h / 20 °C / Inert atmosphere 3.1: methanol; diethyl methoxy borane; sodium tetrahydroborate / tetrahydrofuran / 2.5 h / -80 - -70 °C / Inert atmosphere 4.1: methanesulfonic acid / 20 °C 5.1: palladium 10% on activated carbon; hydrogen / ethanol / 20 °C / 750.08 - 1500.15 Torr / Autoclave View Scheme
Multi-step reaction with 3 steps 1.1: (S)-5-benzyl 2,2,3-trimethyl-4-thione / ethanol / 0.5 h / 0 °C 1.2: 3 h / 0 - 30 °C 2.1: camphor-10-sulfonic acid / ethyl acetate / 4 h / 20 °C 3.1: palladium 10% on activated carbon; hydrogen / ethyl acetate / 5 h / 20 °C View Scheme

(3R,5S)-tert-butyl 6-(tert-butyldiphenylsilyloxy)-3,5-dihydroxyhexanoate (124655-07-8) → 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 70 percent / p-toluenesulfonic acid / acetone / 2 h / 23 °C 2: 80 percent / Bu4NF / tetrahydrofuran / 3 h / 0 °C View Scheme

(5S)-6-(tert-butyl-diphenylsilanyloxy)-5-hydroxy-3-oxohexanoic acid tert-butyl ester (124655-06-7) → 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1). Et3B; 2.) NaBH4, MeOH / 1.) THF, 23 deg C, 15 min; 2.) -70 deg C 2: 70 percent / p-toluenesulfonic acid / acetone / 2 h / 23 °C 3: 80 percent / Bu4NF / tetrahydrofuran / 3 h / 0 °C View Scheme

1-methyl 6-tert.-butyl (2S,4R)-2,4-O-isopropylidene-2,4-dihydroxyadipate (140387-94-6) → 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0)

Conditions	Yield
With hydrogenchloride; sodium borohydrid; ammonium chloride In tetrahydrofuran; methanol
With hydrogenchloride; sodium borohydrid; ammonium chloride In methanol

C13H25ClO4Si → 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: hydrogenchloride / water / 1 h / 0 °C 2.1: sodium tetrahydroborate / water / 14 h / 0 °C 3.1: acetone / 0.25 h / 25 °C 3.2: 6 h / 48 - 50 °C 4.1: 1-methyl-pyrrolidin-2-one / 24 h / 25 - 95 °C 5.1: potassium carbonate; methanol / 0.5 h View Scheme
Multi-step reaction with 5 steps 1.1: hydrogenchloride / water / 1 h / 0 °C 2.1: diethyl methoxy borane / tetrahydrofuran; methanol / 1 h / 25 °C / Inert atmosphere 2.2: 4 h / -78 °C / Inert atmosphere 3.1: acetone / 0.25 h 3.2: 6 h / 48 - 50 °C 4.1: 1-methyl-pyrrolidin-2-one / 24 h / 25 - 95 °C 5.1: potassium carbonate; methanol / 0.5 h View Scheme
Multi-step reaction with 5 steps 1.1: hydrogenchloride / water / 1 h / 0 °C 2.1: sodium tetrahydroborate; sodium dodecyl-sulfate / water / 14 h / 0 °C 3.1: acetone / 0.25 h 3.2: 6 h / 48 - 50 °C 4.1: 1-methyl-pyrrolidin-2-one / 24 h / 25 - 95 °C 5.1: potassium carbonate; methanol / 0.5 h View Scheme
Multi-step reaction with 5 steps 1: hydrogenchloride / water / 1 h / 0 °C 2: sodium tetrahydroborate / water / 14 h / 0 °C 3: (R)-10-camphorsulfonic acid / dichloromethane / 3 h / 40 °C 4: 1-methyl-pyrrolidin-2-one / 24 h / 25 - 95 °C 5: potassium carbonate; methanol / 0.5 h View Scheme

(5S)-tert-butyl 6-chloro-3,5-dihydroxyhexanoate (406680-96-4) → 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: acetone / 0.25 h / 25 °C 1.2: 6 h / 48 - 50 °C 2.1: 1-methyl-pyrrolidin-2-one / 24 h / 25 - 95 °C 3.1: potassium carbonate; methanol / 0.5 h View Scheme
Multi-step reaction with 3 steps 1: (R)-10-camphorsulfonic acid / dichloromethane / 3 h / 40 °C 2: 1-methyl-pyrrolidin-2-one / 24 h / 25 - 95 °C 3: potassium carbonate; methanol / 0.5 h View Scheme

tert-butyl 2-((6S)-6-(chloromethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate → 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1-methyl-pyrrolidin-2-one / 24 h / 25 - 85 °C 2: potassium carbonate; methanol / 0.5 h View Scheme
Multi-step reaction with 3 steps 1: hydrogenchloride / water; dichloromethane / 24 h / 20 °C 2: 1-methyl-pyrrolidin-2-one / 24 h / 25 - 95 °C 3: potassium carbonate; methanol / 0.5 h View Scheme

Tert-butyl (5S)-6-chloro-5-hydroxy-3-oxohexanoate (154026-92-3) → 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sodium tetrahydroborate / water / 14 h / 0 °C 2.1: acetone / 0.25 h / 25 °C 2.2: 6 h / 48 - 50 °C 3.1: 1-methyl-pyrrolidin-2-one / 24 h / 25 - 95 °C 4.1: potassium carbonate; methanol / 0.5 h View Scheme
Multi-step reaction with 4 steps 1.1: diethyl methoxy borane / tetrahydrofuran; methanol / 1 h / 25 °C / Inert atmosphere 1.2: 4 h / -78 °C / Inert atmosphere 2.1: acetone / 0.25 h 2.2: 6 h / 48 - 50 °C 3.1: 1-methyl-pyrrolidin-2-one / 24 h / 25 - 95 °C 4.1: potassium carbonate; methanol / 0.5 h View Scheme
Multi-step reaction with 4 steps 1.1: sodium tetrahydroborate; sodium dodecyl-sulfate / water / 14 h / 0 °C 2.1: acetone / 0.25 h 2.2: 6 h / 48 - 50 °C 3.1: 1-methyl-pyrrolidin-2-one / 24 h / 25 - 95 °C 4.1: potassium carbonate; methanol / 0.5 h View Scheme

1,1-dimethylethyl (3R,5S)-6-chloro-3,5-dihydroxy-4-hexanoate (154026-93-4) → 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: acetone / 0.25 h 1.2: 6 h / 48 - 50 °C 2.1: 1-methyl-pyrrolidin-2-one / 24 h / 25 - 95 °C 3.1: potassium carbonate; methanol / 0.5 h View Scheme
Multi-step reaction with 3 steps 1: (1S)-10-camphorsulfonic acid / acetone / 6 h / 48 - 50 °C 2: 1-methyl-pyrrolidin-2-one / 24 h / 95 °C 3: methanol; potassium carbonate / 20 °C View Scheme

tert-butyl 2-((6S)-6-(acetoxymethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate → 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogenchloride / water; dichloromethane / 48 h / 25 °C 2: potassium carbonate; methanol / 0.5 h View Scheme

(4R-cis)-6-(chloromethyl)-2,2-dimethyl-1,3-dioxane-4-acetic acid,1,1-dimethylethyl ester (154026-94-5) → 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1-methyl-pyrrolidin-2-one / 24 h / 95 °C 2: methanol; potassium carbonate / 20 °C View Scheme

tert-butyl (S)-4-(propylene oxide-2-yl)-3-oxobutanoate (623566-51-8) → 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0)

Conditions

Yield

Multi-step reaction with 4 steps 1.1: sodium hydride / N,N-dimethyl-formamide / 2 h / 20 °C / Inert atmosphere 1.2: 6 h / 20 °C / Inert atmosphere 2.1: methanol; diethyl methoxy borane; sodium tetrahydroborate / tetrahydrofuran / 2.5 h / -80 - -70 °C / Inert atmosphere 3.1: methanesulfonic acid / 20 °C 4.1: palladium 10% on activated carbon; hydrogen / ethanol / 20 °C / 750.08 - 1500.15 Torr / Autoclave View Scheme

1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0) → 2-((4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-1,3-dioxane-4-yl)acetic acid (154877-92-6)

Conditions	Yield
Stage #1: 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate With water; sodium hydroxide In methanol at 40 - 50℃; Stage #2: With hydrogenchloride In water at 15 - 20℃; pH=4 - 4.2;	100%
With sodium hydroxide In tetrahydrofuran Reflux;
With sodium hydroxide In tetrahydrofuran Reflux;

1H-imidazole (288-32-4) + ethyl acetate dichloromethane + 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0) → (3R,5S)-6-iodo-3,5-O-isopropylidene-3,5-dihydroxyhexanoic acid tert-butyl ester (134742-42-0)

Conditions	Yield
With iodine; triphenylphosphine In benzene	99%

1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0) → C13H24O5

Conditions	Yield
With toluene-4-sulfonic acid In acetone at 50℃;	99%

1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0) → tert-butyl 2-[(4R,6S)-6-formyl-2,2-dimethyl-1,3-dioxan-4-yl]acetate (124752-23-4)

Conditions	Yield
Swern oxidation; (further oxidizing agents);	97%
Stage #1: 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate With dimethyl sulfoxide; N-ethyl-N,N-diisopropylamine In dichloromethane at -5 - 0℃; for 0.5h; Stage #2: With pyridine; sulfur trioxide pyridine complex; dimethyl sulfoxide In dichloromethane at -5 - 20℃; for 1.16667h;	93%
With sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; potassium bromide In dichloromethane; water at 5 - 10℃; for 0.166667h; Temperature; Flow reactor;	93.5%

1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0) + methanesulfonyl chloride (124-63-0) → (3R,5S)-6-<(methylsulfonyl)oxy>-3,5-O-isopropylidene-3,5-dihydroxyhexanoic acid tert-butyl ester (135054-68-1)

Conditions	Yield
With pyridine In dichloromethane at 0℃; for 0.5h;	90%
With pyridine In dichloromethane; toluene
With triethylamine In dichloromethane	100 g

C20H19FN2O3 (906645-38-3) + 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0) → C33H41FN2O7 (906645-40-7)

Conditions	Yield
With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at -5 - 20℃; Mitsunobu reaction;	88%

1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0) + benzoyl chloride (98-88-4) → ((4S,6R)-6-(2-tert-butoxy-2-oxoethyl)-2,2-dimethyl-1,3-dioxan-4-yl)methyl benzoate (131666-50-7)

Conditions	Yield
Stage #1: 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate With pyridine In dichloromethane at 20℃; for 0.5h; Stage #2: benzoyl chloride In dichloromethane at 20℃; for 1h;	88%

1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0) + acetyl chloride (75-36-5) → (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester (154026-95-6)

Conditions	Yield
Stage #1: 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate With pyridine In dichloromethane at 20℃; for 0.5h; Stage #2: acetyl chloride In dichloromethane at 20℃; for 1h;	86%
With pyridine In dichloromethane at 20℃; for 0.5h;	15.9 g

2-methyl-2-phenylpropionic acid (826-55-1) + 1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0) → C22H34O5

Conditions	Yield
With 2,4,6-trimethyl-pyridine; tetrabutylammonium perchlorate; silver perchlorate In dichloromethane at 20℃; for 3h; Electrolysis; Molecular sieve;	52%

1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0) + ethyl (triphenylphosphoranylidene)acetate (1099-45-2) → C17H28O6 (707542-98-1)

Conditions	Yield
With manganese(IV) oxide In toluene for 17h; Heating / reflux;	41%

1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0) → C40H44F2N2O5

Conditions	Yield
Multi-step reaction with 2 steps 1: 46 percent / n-BuLi / 2 h / -78 - 25 °C View Scheme

1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0) → (6-{2-[3-(4-fluorophenyl)-1-isopropyl-5-(4-methoxybenzylcarbamoyl)-4-phenyl-1H-pyrrol-2-yl]vinyl}-2,2-dimethyl-[1,3]dioxan-4-yl)acetic acid tert-butyl ester (855249-03-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 75 percent / NaHMDS / tetrahydrofuran / 2 h / -78 - 25 °C View Scheme

1,1-dimethylethyl (4R-cis)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (124655-09-0) → C42H51FN2O6

Conditions	Yield
Multi-step reaction with 3 steps 1: 75 percent / NaHMDS / tetrahydrofuran / 2 h / -78 - 25 °C 2: hydrogen / Pd/C / methanol / 3 h / 25 °C / 2585.81 Torr View Scheme

Upstream product

• 154026-95-6 (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester 
• 1067638-10-1 C₁₈H₃₂O₆ 
• 140387-94-6 1-methyl 6-tert.-butyl (2S,4R)-2,4-O-isopropylidene-2,4-dihydroxyadipate 
• 124655-06-7 (5S)-6-(tert-butyl-diphenylsilanyloxy)-5-hydroxy-3-oxohexanoic acid tert-butyl ester 
• 124655-07-8 (3R,5S)-tert-butyl 6-(tert-butyldiphenylsilyloxy)-3,5-dihydroxyhexanoate 
• 540-88-5 acetic acid tert-butyl ester 
• 143800-10-6 [(4R,6S)-2,2-Dimethyl-6-((2S,3S)-3-trimethylsilanyl-oxiranyl)-[1,3]dioxan-4-yl]-acetic acid tert-butyl ester 
• 143840-67-9 (S)-5-Hydroxy-3-oxo-5-((2S,3S)-3-trimethylsilanyl-oxiranyl)-pentanoic acid tert-butyl ester 
• 143827-05-8 (3R,5S)-3,5-Dihydroxy-5-((2S,3S)-3-trimethylsilanyl-oxiranyl)-pentanoic acid tert-butyl ester 
• 1694-31-1 tert-butyl acetoacetate 
• 147488-98-0 isopropyl (2S,3S)-7-t-butoxycarbonyl-2,3-bis(t-butyldimethylsilyloxy)-4,6-dioxoheptanoate 
• 147488-99-1 isopropyl (2S,3S,6R)-7-t-butoxycarbonyl-2,3-bis(t-butyldimethylsilyloxy)-6-hydroxy-4-oxoheptanoate 
• 147489-01-8 isopropyl (2S,3R,4S,6R)-7-t-butpxycarbonyl-2,3-bis(t-butyldimethylsilyloxy)-4,6-isopropylidenedioxyheptanoate 
• 147489-00-7 isopropyl (2S,3R,4S,6R)-7-t-butoxycarbonyl-2,3-bis(t-butyldimethylsilyloxy)-4,6-dihydroxyheptanoate 

Downstream Products

• 124752-23-4 tert-butyl 2-[(4R,6S)-6-formyl-2,2-dimethyl-1,3-dioxan-4-yl]acetate 
• 141942-87-2 [(4R,6S)-6-(4-Chloro-benzenesulfonyloxymethyl)-2,2-dimethyl-[1,3]dioxan-4-yl]-acetic acid tert-butyl ester 
• 154026-95-6 (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid tert-butyl ester 
• 143840-61-3 tert-butyl 2-((4R, 6S)-2,2-dimethyl-6-((E)-styryl)-1,3-dioxan-4-yl)acetate 
• 862994-56-7 E-7-[2-(N-methyl-N-methanesulfonylamino)-4-(4-fluorophenyl)-6-isopropyl-pyrimidin-5-yl]-(3R,5S)-3,5-dihydroxyhept-6-enoic acid diisopropylamine salt 
• 1353637-19-0 (3R,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxyhept-6-enoic acid diisopropylamine salt 
• 917805-74-4 (3R,5S,6E)-7-[4-(4-fluorophenyl)-2-[methyl(methylsulfonyl)amino]-6-(propan-2-yl)pyrimidin-5-yl]-3,5-dihydroxyhept-6-enoic acid-2-methylpropan-2-amine 
• 147489-06-3 (4R,6S)-(E)-{6-[2-(2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl)-vinyl]-2,2-dimethyl-1,3-dioxan-4-yl}acetic acid tert-butyl ester 
• 136034-04-3 Sodium 3(R),5(S)-dihydroxy-6-[(2-p-fluorophenyl-4-p-fluorophenylthio-6-isopropyl)phenoxy]hexanoate 
• 135054-69-2 {(4R,6S)-6-[4'-Fluoro-5-(4-fluoro-phenylsulfanyl)-3-isopropyl-biphenyl-2-yloxymethyl]-2,2-dimethyl-[1,3]dioxan-4-yl}-acetic acid tert-butyl ester 
• 135054-70-5 tert.-Butyl 3(R),5(S)-dihydroxy-6-[(2-p-fluorophenyl-4-p-fluorophenylthio-6-isopropyl)phenoxy]hexanoate 
• 135054-71-6 4(R)-Hydroxy-6(S)-[(2-p-fluorophenyl-4-p-fluorophenylthio-6-isopropyl)phenoxymethyl]-3,4,5,6-tetrahydro-2H-pyran-2-one 
• 125971-94-0 2-((4R, 6R)-6-cyanomethyl-2,2-dimethyl-1,3-dioxan-4-yl)acetic acid tert-butyl ester 
• 855249-04-6 (3R,5R)-7-[3-(4-fluoro-phenyl)-1-isopropyl-5-(4-methoxy-benzylcarbamoyl)-4-phenyl-1H-pyrrol-2-yl]-3,5-dihydroxy-heptanoic acid tert-butyl ester 

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