112849-27-1

Basic information

• Product Name: Bis-TBDMS-trans-calcipotriol
• Synonyms: BIS-TBDMS-TRANS-CALCIPOTRIOL;24-Cycloproyply-1,3-bis[[(1,1-dimethylethyl)dimethylsily]oxy]-9,10-secochola-5,7,10(19),22-tetraen-24-ol;Cyclopropanemethanol, a-[(1E,3R)-3-[(1R,3aS,4E,7aR)-4-[(2E)-2-[(3S,5R)-3,5-bis[[(1,1-dimethylethyl)dimethylsilyl]oxy]-2-methylenecyclohexylidene]ethylidene]octahydro-7a-methyl-1H-inden-1-yl]-1-buten-1-yl]-, (aS)-;Trans-Calcipotriol-bis-TBDMS-ether;Bis-O-(tert-butyldimethylsilyl)-trans-calcipotriol;(αS)-α-[(1E,3R)-3-[(1R,3aS,4E,7aR)-4-[(2E)-2-[(3S,5R)-3,5-Bis[[(1,1-diMethylethyl)diMethylsilyl]oxy]-2-Methylenecyclohexylidene]ethylidene]octahydro-7a-Methyl-1H-inden-1-yl]-1-buten-1-yl]cyclopropaneMetha;(1S,4R,E)-4-((1R,3aS,7aR,E)-4-((E)-2-((3S,5R)-3,5-bis(tert-butyldiMethylsilyloxy)-2-Methylenecyclohexylidene)ethylidene)-7a-Methyloctahydro-1H-inden-1-yl)-1-cyclopropylpent-2-en-1-ol;Calcipotriol Impurity 10
• CAS NO: 112849-27-1
• Molecular Formula: C₃₉H₆₈O₃Si₂
• Molecular Weight: 641.135
• EINECS: 1312995-182-4
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 112849-27-1.mol

Chemical Properties

• Boiling Point: 628.182 °C at 760 mmHg
• Flash Point: 333.713 °C
• Appearance: /
• Density: 0.988 g/cm³
• Refractive Index: 1.515
• Storage Temp.: Amber Vial, -20°C Freezer, Under Inert Atmosphere
• Solubility: Dichloromethane, Ethyl Acetate
• PKA: 14.29±0.20(Predicted)
• CAS DataBase Reference: Bis-TBDMS-trans-calcipotriol(CAS DataBase Reference)
• NIST Chemistry Reference: Bis-TBDMS-trans-calcipotriol(112849-27-1)
• EPA Substance Registry System: Bis-TBDMS-trans-calcipotriol(112849-27-1)

Safety Data

• Hazardous Substances Data: 112849-27-1(Hazardous Substances Data)

Usage

Chemical Properties

Clear Oil

Uses

Protected trans-Calcipotriol, a vitamin D analog.

InChI:InChI=1/C39H68O3Si2/c1-27(16-23-35(40)30-18-19-30)33-21-22-34-29(15-14-24-39(33,34)9)17-20-31-25-32(41-43(10,11)37(3,4)5)26-36(28(31)2)42-44(12,13)38(6,7)8/h16-17,20,23,27,30,32-36,40H,2,14-15,18-19,21-22,24-26H2,1,3-13H3/b23-16+,29-17+,31-20+/t27-,32-,33-,34+,35-,36?,39?/m1/s1

Synthetic route

1(S),3(R)-bis(tert-butyldimethylsilyloxy)-20(R)-(3’-cyclopropyl-3’-oxypropyl-1’(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-17-9) → (1S,3R,3'R)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-26-0) + (1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1)

Conditions	Yield
With sodium tetrahydroborate; cerium(III) chloride In methanol further reag.: (S)-BINAL-H;	A 55% B 33%
Stage #1: 1(S),3(R)-bis(tert-butyldimethylsilyloxy)-20(R)-(3’-cyclopropyl-3’-oxypropyl-1’(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene With borane N,N-diethylaniline complex; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole In tetrahydrofuran; toluene at 0 - 5℃; for 2.66667 - 3.58333h; Stage #2: With water; sodium hydrogencarbonate In tetrahydrofuran; toluene at 0 - 5℃;

(1S,3R,3'R)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-26-0) → (1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1)

Conditions	Yield
With sulfuric acid In tetrahydrofuran; water at 20℃; pH=1.7;	45%
With sodium hydrogen sulfate In tetrahydrofuran; water; acetone at 20 - 25℃; for 3.66667h; pH=1.58;
With sulfuric acid In water; ethyl acetate; acetone at 27℃; for 0.583333h; pH=1.25;
With phosphoric acid In tetrahydrofuran; water; acetone at 20℃; for 19h; pH=1.48;
With phosphoric acid In tetrahydrofuran; water; acetone at 30℃; for 6h; pH=1.01;

Cyclopropyl methyl ketone (765-43-5) → (1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1)

Conditions	Yield
Multi-step reaction with 7 steps 1: 87 percent / bromine / methanol / 0.5 h / Ambient temperature 2: 84 percent 3: 86 percent / 2N sodium hydroxide / H2O; CH2Cl2 5: N-methylmorpholine N-oxide, selenium dioxide 6: imidazole / dimethylformamide 7: 33 percent / NaBH4, CeCl3*6H2O / methanol / further reag.: (S)-BINAL-H View Scheme
Multi-step reaction with 5 steps 1: 87 percent / bromine / methanol / 0.5 h / Ambient temperature 2: 84 percent 3: 86 percent / 2N sodium hydroxide / H2O; CH2Cl2 4: dimethylsulfoxide / 4 h / 105 °C 5: 33 percent / NaBH4, CeCl3*6H2O / methanol / further reag.: (S)-BINAL-H View Scheme

2-bromo-1-cyclopropylethan-1-one (69267-75-0) → (1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1)

Conditions	Yield
Multi-step reaction with 6 steps 1: 84 percent 2: 86 percent / 2N sodium hydroxide / H2O; CH2Cl2 4: N-methylmorpholine N-oxide, selenium dioxide 5: imidazole / dimethylformamide 6: 33 percent / NaBH4, CeCl3*6H2O / methanol / further reag.: (S)-BINAL-H View Scheme
Multi-step reaction with 4 steps 1: 84 percent 2: 86 percent / 2N sodium hydroxide / H2O; CH2Cl2 3: dimethylsulfoxide / 4 h / 105 °C 4: 33 percent / NaBH4, CeCl3*6H2O / methanol / further reag.: (S)-BINAL-H View Scheme

1-cyclopropyl-2-(triphenyl-λ5-phosphanylidene)ethan-1-one (7691-76-1) → (1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1)

Conditions	Yield
Multi-step reaction with 4 steps 2: N-methylmorpholine N-oxide, selenium dioxide 3: imidazole / dimethylformamide 4: 33 percent / NaBH4, CeCl3*6H2O / methanol / further reag.: (S)-BINAL-H View Scheme
Multi-step reaction with 2 steps 1: dimethylsulfoxide / 4 h / 105 °C 2: 33 percent / NaBH4, CeCl3*6H2O / methanol / further reag.: (S)-BINAL-H View Scheme

tert-butyldimethylsilyl chloride (18162-48-6) → (1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1)

Conditions	Yield
Multi-step reaction with 7 steps 1: 42 percent / imidazole / dimethylformamide / 1.5 h / 20 °C 2: 1.) ozone 2.) PPh3 / 1.) CH2Cl2, MeOH, -60 deg C 2.) CH2Cl2, MeOH, -60 to 0 deg C 3: NaHCO3 / aq. ethanol / Heating 5: N-methylmorpholine N-oxide, selenium dioxide 6: imidazole / dimethylformamide 7: 33 percent / NaBH4, CeCl3*6H2O / methanol / further reag.: (S)-BINAL-H View Scheme
Multi-step reaction with 7 steps 1: 52 percent / imidazole / dimethylformamide / 1.5 h / 20 °C 2: 1.) ozone 2.) PPh3 / 1.) CH2Cl2, MeOH, -60 deg C 2.) CH2Cl2, MeOH, -60 to 0 deg C 3: NaHCO3 / aq. ethanol / Heating 5: N-methylmorpholine N-oxide, selenium dioxide 6: imidazole / dimethylformamide 7: 33 percent / NaBH4, CeCl3*6H2O / methanol / further reag.: (S)-BINAL-H View Scheme

3(R)-(tert-butyldimethylsilyloxy)-20(S)-formyl-9,10-secopregna-5(Z),7(E),10(19)-triene (112828-12-3) → (1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1)

Conditions	Yield
Multi-step reaction with 4 steps 2: N-methylmorpholine N-oxide, selenium dioxide 3: imidazole / dimethylformamide 4: 33 percent / NaBH4, CeCl3*6H2O / methanol / further reag.: (S)-BINAL-H View Scheme

(S)-3-[(1R,3aS,7aR)-7a-Methyl-1-((E)-(1R,4R)-1,4,5-trimethyl-hex-2-enyl)-octahydro-inden-(4E)-ylidenemethyl]-2,2-dioxo-2,3,4,5,6,7-hexahydro-1H-2λ6-benzo[c]thiophen-5-ol (87680-65-7) → (1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1)

Conditions	Yield
Multi-step reaction with 7 steps 1: 42 percent / imidazole / dimethylformamide / 1.5 h / 20 °C 2: 1.) ozone 2.) PPh3 / 1.) CH2Cl2, MeOH, -60 deg C 2.) CH2Cl2, MeOH, -60 to 0 deg C 3: NaHCO3 / aq. ethanol / Heating 5: N-methylmorpholine N-oxide, selenium dioxide 6: imidazole / dimethylformamide 7: 33 percent / NaBH4, CeCl3*6H2O / methanol / further reag.: (S)-BINAL-H View Scheme
Multi-step reaction with 7 steps 1: 52 percent / imidazole / dimethylformamide / 1.5 h / 20 °C 2: 1.) ozone 2.) PPh3 / 1.) CH2Cl2, MeOH, -60 deg C 2.) CH2Cl2, MeOH, -60 to 0 deg C 3: NaHCO3 / aq. ethanol / Heating 5: N-methylmorpholine N-oxide, selenium dioxide 6: imidazole / dimethylformamide 7: 33 percent / NaBH4, CeCl3*6H2O / methanol / further reag.: (S)-BINAL-H View Scheme

20(R),3(R)-(tert-butyldimethylsilyloxy)-20-(3'-cyclopropyl-3'-oxoprop-1'(E)-enyl)-9,10-secopregna-5(Z),7(E),10(19)-triene (112849-18-0) → (1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: N-methylmorpholine N-oxide, selenium dioxide 2: imidazole / dimethylformamide 3: 33 percent / NaBH4, CeCl3*6H2O / methanol / further reag.: (S)-BINAL-H View Scheme

(E)-(R)-4-{(1R,3aS,7aR)-4-[2-[(R)-5-(tert-Butyl-dimethyl-silanyloxy)-3-hydroxy-2-methylene-cyclohex-(E)-ylidene]-eth-(E)-ylidene]-7a-methyl-octahydro-inden-1-yl}-1-cyclopropyl-pent-2-en-1-one → (1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: imidazole / dimethylformamide 2: 33 percent / NaBH4, CeCl3*6H2O / methanol / further reag.: (S)-BINAL-H View Scheme

(2-cyclopropyl-2-oxoethyl) (triphenyl)phosphonium bromide (112849-15-7) → (1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1)

Conditions	Yield
Multi-step reaction with 5 steps 1: 86 percent / 2N sodium hydroxide / H2O; CH2Cl2 3: N-methylmorpholine N-oxide, selenium dioxide 4: imidazole / dimethylformamide 5: 33 percent / NaBH4, CeCl3*6H2O / methanol / further reag.: (S)-BINAL-H View Scheme
Multi-step reaction with 3 steps 1: 86 percent / 2N sodium hydroxide / H2O; CH2Cl2 2: dimethylsulfoxide / 4 h / 105 °C 3: 33 percent / NaBH4, CeCl3*6H2O / methanol / further reag.: (S)-BINAL-H View Scheme

(7Z)-Vitamin D2 (247900-07-8) → (1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1)

Conditions	Yield
Multi-step reaction with 8 steps 1: liq. SO2 / 0.5 h / Heating 2: 42 percent / imidazole / dimethylformamide / 1.5 h / 20 °C 3: 1.) ozone 2.) PPh3 / 1.) CH2Cl2, MeOH, -60 deg C 2.) CH2Cl2, MeOH, -60 to 0 deg C 4: NaHCO3 / aq. ethanol / Heating 6: N-methylmorpholine N-oxide, selenium dioxide 7: imidazole / dimethylformamide 8: 33 percent / NaBH4, CeCl3*6H2O / methanol / further reag.: (S)-BINAL-H View Scheme
Multi-step reaction with 8 steps 1: liq. SO2 / 0.5 h / Heating 2: 52 percent / imidazole / dimethylformamide / 1.5 h / 20 °C 3: 1.) ozone 2.) PPh3 / 1.) CH2Cl2, MeOH, -60 deg C 2.) CH2Cl2, MeOH, -60 to 0 deg C 4: NaHCO3 / aq. ethanol / Heating 6: N-methylmorpholine N-oxide, selenium dioxide 7: imidazole / dimethylformamide 8: 33 percent / NaBH4, CeCl3*6H2O / methanol / further reag.: (S)-BINAL-H View Scheme

3(S)-tert-butyldimethylsilyloxy-20(S)-formyl-9,10-secoprega-5,7(E),10(19)-triene (87407-47-4) → (1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1)

Conditions	Yield
Multi-step reaction with 5 steps 1: NaHCO3 / aq. ethanol / Heating 3: N-methylmorpholine N-oxide, selenium dioxide 4: imidazole / dimethylformamide 5: 33 percent / NaBH4, CeCl3*6H2O / methanol / further reag.: (S)-BINAL-H View Scheme

3(S)-tert-butyldimethylsilyloxy-20(S)-formyl-9,10-secoprega-5,7(E),10(19)-triene (87422-13-7) → (1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1)

Conditions	Yield
Multi-step reaction with 5 steps 1: NaHCO3 / aq. ethanol / Heating 3: N-methylmorpholine N-oxide, selenium dioxide 4: imidazole / dimethylformamide 5: 33 percent / NaBH4, CeCl3*6H2O / methanol / further reag.: (S)-BINAL-H View Scheme

(3S,6R)-(tert-butyldimethylsilyloxy)-9,10-seco-ergosta-5,7(E),10(19),22(E)-tetraene SO2 adduct (87417-26-3) → (1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1)

Conditions	Yield
Multi-step reaction with 6 steps 1: 1.) ozone 2.) PPh3 / 1.) CH2Cl2, MeOH, -60 deg C 2.) CH2Cl2, MeOH, -60 to 0 deg C 2: NaHCO3 / aq. ethanol / Heating 4: N-methylmorpholine N-oxide, selenium dioxide 5: imidazole / dimethylformamide 6: 33 percent / NaBH4, CeCl3*6H2O / methanol / further reag.: (S)-BINAL-H View Scheme

(3S,6S)-(tert-butyldimethylsilyloxy)-9,10-seco-ergosta-5,7(E),10(19),22(E)-tetraene SO2-adduct (87417-26-3, 87417-27-4) → (1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1)

Conditions	Yield
Multi-step reaction with 6 steps 1: 1.) ozone 2.) PPh3 / 1.) CH2Cl2, MeOH, -60 deg C 2.) CH2Cl2, MeOH, -60 to 0 deg C 2: NaHCO3 / aq. ethanol / Heating 4: N-methylmorpholine N-oxide, selenium dioxide 5: imidazole / dimethylformamide 6: 33 percent / NaBH4, CeCl3*6H2O / methanol / further reag.: (S)-BINAL-H View Scheme

C42H72O4Si2 → (1S,3R,3'R)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-26-0) + (1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1)

Conditions	Yield
Stage #1: C42H72O4Si2 With silica gel In hexane; ethyl acetate at 20℃; Reaction on a column; Stage #2: With potassium carbonate In tetrahydrofuran; methanol Product distribution / selectivity;	A n/a B n/a

C46H71NO6Si2 → (1S,3R,3'R)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-26-0) + (1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1)

Conditions	Yield
With silica gel In hexane; ethyl acetate Product distribution / selectivity; Mitsunobu reaction;

C41H70O4Si2 → (1S,3R,3'R)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-26-0) + (1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1)

Conditions	Yield
With silica gel In hexane at 0 - 40℃; for 2.5 - 26h; Product distribution / selectivity;	A n/a B n/a
With silica gel; potassium carbonate In hexane for 48h; Product distribution / selectivity;
With silica gel; triethylamine In hexane for 7h; Product distribution / selectivity;

1(S),3(R)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-oxoprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene SO2-adducts → (1S,3R,3'R)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-26-0) + (1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1)

Conditions	Yield
Stage #1: 1(S),3(R)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-oxoprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene SO2-adducts With borane Ν,Ν-diethylaniline complex; (1S,2R)-1-amino-2-indanol In tert-butyl methyl ether; toluene at 10 - 25℃; for 0.5 - 1h; Stage #2: With hydrogenchloride In tert-butyl methyl ether; water; toluene at 10 - 15℃; Stage #3: With sodium hydrogencarbonate In water at 90℃; for 2 - 2.5h; Product distribution / selectivity;
Stage #1: 1(S),3(R)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-oxoprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene SO2-adducts With dimethylsulfide borane complex; (1S,2R)-1-amino-2-indanol In tert-butyl methyl ether; toluene at 15 - 20℃; for 0.5 - 1h; Stage #2: With hydrogenchloride In tert-butyl methyl ether; water; toluene at 10 - 15℃; Stage #3: With sodium hydrogencarbonate In water at 90℃; for 2 - 2.5h; Product distribution / selectivity;
Stage #1: 1(S),3(R)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-oxoprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene SO2-adducts With borane Ν,Ν-diethylaniline complex; (R)-α,α-diphenylprolinol In tert-butyl methyl ether; toluene at 15 - 20℃; for 0.5 - 1h; Stage #2: With hydrogenchloride In tert-butyl methyl ether; water; toluene at 10 - 15℃; Stage #3: With sodium hydrogencarbonate In water at 90℃; for 2 - 2.5h; Product distribution / selectivity;

SO2-adduct of 1(S),3(R)-bis(tert-butyl-dimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'(S)-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene + SO2-adduct of 1(S),3(R)-bis(tert-butyl-dimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'(R)-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (878285-87-1) → (1S,3R,3'R)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-26-0) + (1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1)

Conditions	Yield
With sodium hydrogencarbonate In water at 90℃; for 2 - 2.5h; Retro Diels-Alder Reaction;

C39H70O5SSi2 + C39H70O5SSi2 + C39H70O5SSi2 + C39H70O5SSi2 → (1S,3R,3'R)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-26-0) + (1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1)

Conditions	Yield
With sodium hydrogencarbonate In tert-butyl methyl ether; water; toluene at 90℃; for 2 - 2.5h; retro Diels-Alder Reaction;

(1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1) → (1S,3R)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'(S)-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(Z),7(E),10(19)-triene (112875-61-3)

Conditions	Yield
With anthracene; triethylamine In toluene at 20℃; for 1h; Irradiation;
With 9-acetylanthracene; triethylamine In toluene at 5 - 8℃; for 0.75h; UV-irradiation;
With 9-acetylanthracene In toluene at 20℃; UV-irradiation;
9-acetylanthracene In tert-butyl methyl ether at 10℃; Industry scale; Irradiation;
With anthracene; triethylamine In toluene at 20 - 25℃; UV-irradiation;

(1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1) → (1S,3R,1'S,2'S,3'S)-(3'-cyclopropyl-1',2'-epoxy-3'-hydroxypropyl)-9,10-secopregna-5(E),7(E),10(19)-triene (115540-29-9, 115540-30-2, 115540-31-3, 115598-01-1)

Conditions	Yield
With titanium(IV) isopropylate; tert.-butylhydroperoxide; (+)-Weinsaeure-diethylester In dichloromethane at -20℃; further reag.: (-)-diethyl tartrate; Yield given;

(1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1) → (1S,3R,1'S,2'S,3'S)-(3'-cyclopropyl-1',2'-epoxy-3'-hydroxypropyl)-9,10-secopregna-5(E),7(E),10(19)-triene (115540-29-9, 115540-30-2, 115540-31-3, 115598-01-1) + (1S,3R,1'R,2'R,3'S)-(3'-cyclopropyl-1',2'-epoxy-3'-hydroxypropyl)-9,10-secopregna-5(E),7(E),10(19)-triene (115540-29-9, 115540-30-2, 115540-31-3, 115598-01-1)

Conditions	Yield
With titanium(IV) isopropylate; tert.-butylhydroperoxide; (-)-diethyl tartrate In dichloromethane at -20℃; further reag.: (+)-diethyl tartrate; Yield given. Yields of byproduct given;

(1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1) → calcipotriene (112965-21-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: anthracene, triethylamine / toluene / 1 h / 20 °C / Irradiation 2: 73 percent / tetrabutylammonium fluoride / tetrahydrofuran / 0.83 h / 60 °C View Scheme

vinyl acetate (108-05-4) + (1S,3R,3'R)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-26-0) + (1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1) → C41H70O4Si2

Conditions	Yield
Alcaligenes sp. lipase In hexane at 22 - 28℃; for 3h; Enzymatic reaction;	n/a
Alcaligenes sp. lipase In di-isopropyl ether at 20℃; for 2h; Enzymatic reaction;	n/a

(1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1) + 4-nitro-benzoic acid (62-23-7) → C46H71NO6Si2

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 60℃; for 4.5h; Mitsunobu reaction;	n/a

C41H70O4Si2 (565429-98-3) + (1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1) → (1S,3R,3'R)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-26-0)

Conditions	Yield
With silica gel In hexane for 1.5h; Product distribution / selectivity;

(1S,3R,3'S)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10(19)-triene (112849-27-1) → C39H68O3Si2 + (1S,3R)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'(S)-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(Z),7(E),10(19)-triene (112875-61-3)

Conditions	Yield
9-acetylanthracene In tert-butyl methyl ether at 10℃; Product distribution / selectivity; UV-irradiation;
9-acetylanthracene In tert-butyl methyl ether at 10℃; Product distribution / selectivity; UV-irradiation;

Upstream product

• 765-43-5 Cyclopropyl methyl ketone 
• 18162-48-6 tert-butyldimethylsilyl chloride 
• 112828-12-3 3(R)-(tert-butyldimethylsilyloxy)-20(S)-formyl-9,10-secopregna-5(Z),7(E),10⁽¹⁹⁾-triene 
• 878285-87-1 SO₂-adduct of 1(S),3(R)-bis(tert-butyl-dimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'(R)-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10⁽¹⁹⁾-triene 
• 112849-26-0 (1S,3R,3'R)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10⁽¹⁹⁾-triene 
• 87417-26-3 (3S,6S)-(tert-butyldimethylsilyloxy)-9,10-seco-ergosta-5,7(E),10⁽¹⁹⁾,22(E)-tetraene SO₂-adduct 
• 87417-26-3 (3S,6R)-(tert-butyldimethylsilyloxy)-9,10-seco-ergosta-5,7(E),10⁽¹⁹⁾,22(E)-tetraene SO₂ adduct 
• 87422-13-7 3(S)-tert-butyldimethylsilyloxy-20(S)-formyl-9,10-secoprega-5,7(E),10⁽¹⁹⁾-triene 
• 87407-47-4 3(S)-tert-butyldimethylsilyloxy-20(S)-formyl-9,10-secoprega-5,7(E),10⁽¹⁹⁾-triene 
• 247900-07-8 (7Z)-Vitamin D₂ 
• 112849-15-7 (2-cyclopropyl-2-oxoethyl) (triphenyl)phosphonium bromide 
• 112849-18-0 20(R),3(R)-(tert-butyldimethylsilyloxy)-20-(3'-cyclopropyl-3'-oxoprop-1'(E)-enyl)-9,10-secopregna-5(Z),7(E),10⁽¹⁹⁾-triene 
• 87680-65-7 (S)-3-[(1R,3aS,7aR)-7a-Methyl-1-((E)-(1R,4R)-1,4,5-trimethyl-hex-2-enyl)-octahydro-inden-(4E)-ylidenemethyl]-2,2-dioxo-2,3,4,5,6,7-hexahydro-1H-2λ⁶-benzo[c]thiophen-5-ol 
• 7691-76-1 1-cyclopropyl-2-(triphenyl-λ⁵-phosphanylidene)ethan-1-one 

Downstream Products

• 112875-61-3 (1S,3R)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'(S)-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(Z),7(E),10⁽¹⁹⁾-triene 
• 115540-29-9 (1S,3R,1'S,2'S,3'S)-(3'-cyclopropyl-1',2'-epoxy-3'-hydroxypropyl)-9,10-secopregna-5(E),7(E),10⁽¹⁹⁾-triene 
• 115540-29-9 (1S,3R,1'R,2'R,3'S)-(3'-cyclopropyl-1',2'-epoxy-3'-hydroxypropyl)-9,10-secopregna-5(E),7(E),10⁽¹⁹⁾-triene 
• 112849-26-0 (1S,3R,3'R)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(E),7(E),10⁽¹⁹⁾-triene 
• 112965-21-6 calcipotriene 

Relevant articles and documents

EPIMERIZATION BY STEREOSELECTIVE SYNTHESIS OF VITAMIN D ANALOGUES

A method for epimerization process of C-24 ketones to desired C-24 alcohol by stereo selective reduction using chiral borane reducing agents in the presence of chiral auxillary such as (R)-2-methyl-CBS-oxazaborolidine for the preparation of calcipotriene intermedites and its process to calcipotriene.

EPIMERISATION OF ALLYLIC ALCOHOLS

The present invention relates to processes for epimerising alcohols of compounds having a hydroxyl substituent on an asymmetric allylic carbon, such as compounds useful for the synthesis of vitamin D analogues where the epimeric hydroxyl substituent is at the 24 position. The invention further relates to methods of producing intermediates useful for the synthesis of calcipotriol by said epimerisation processes.

STEREOSELECTIVE SYNTHESIS OF VITAMIN D ANALOGUES

The present invention relates to intermediates useful for the synthesis of calcipotriol or calcipotriol monohydrate, to methods of producing said intermediates, and to methods of stereoselectively reducing said intermediates.

EPIMERIZATION OF ANALOGS OF VITAMIN D

Provided is a method of general applicability of epimerizing a vitamin-D analog having an asymmetric allylic carbon atom at the C-24 position, which comprises the steps of: a) esterifying the hydroxyl group on the asymmetric allylic carbon atom at the 24 position with an esterifying agent, b) contacting a solution of the ester in a solvent with an epimerization-active solid, whereby the ester is epimerized, and c) hydrolysing the epimerized ester to obtain a mixture of C-24 epimers having a hydroxyl substituent on the asymmetric allylic carbon at position 24. The method is of particular utility in making calcipotriene.