39746-01-5

Basic information

• Product Name: (-)-Corey aldehyde benzoate
• Synonyms: BENZOIC ACID (3AR,4R,5R,6AS)-4-FORMYL-2-OXO-HEXAHYDRO-CYCLOPENTA[B]FURAN-5-YL ESTER;[3ar(3aα,4α,5β,6aα)]-(-)-5-(benzoyloxy)hexahydro-2-oxo-2h-cyclopenta[b]furan-4-carboxaldehyde;(-)-Corey aldehyde benzoate;3β-Benzoyloxy-2β-carboxaldehyde-5α-hydroxy-1α-cyclopentaneacetic Acid γ-Lactone;(3AR,4R,5R,6AS)-5-(BENZOYLOXY)HEXAHYDRO-2-OXO-2H-CYCLOPENTA[B]FURAN-4-CARBOXALDEHYDE;[3AR(3A-ALPHA,4ALPHA,5BETA,6A-ALPHA)]-(-)-5-(BENZOYLOXY)HEXAHYDRO-2-OXO-2 H-CYCLOPENTA[B]FURAN-4-CARBOXALDEHYDE;[3ar(3aa,4a,5b,6aa)]-(-)-5-(benzoyloxy)hexahydro-2-oxo-2h-cyclopenta[b]furan-4-carboxaldehyde;COREY ALDEHYDE BENZOATE
• CAS NO: 39746-01-5
• Molecular Formula: C₁₅H₁₄O₅
• Molecular Weight: 274.27
• Mol File: 39746-01-5.mol
• Article Data: 16

Chemical Properties

• Melting Point: 128-138 °C(lit.)
• Boiling Point: 470.427 °C at 760 mmHg
• Flash Point: 211.802 °C
• Appearance: /
• Density: 1.33 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.577
• Storage Temp.: ?20°C
• CAS DataBase Reference: (-)-Corey aldehyde benzoate(CAS DataBase Reference)
• NIST Chemistry Reference: (-)-Corey aldehyde benzoate(39746-01-5)
• EPA Substance Registry System: (-)-Corey aldehyde benzoate(39746-01-5)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 39746-01-5(Hazardous Substances Data)

Usage

Description

Corey lactone aldehyde benzoate is a versatile, chiral intermediate used in the preparation of prostaglandins and prostaglandin analogs.

Uses

(-)-Corey aldehyde benzoate is used in the synthesis of human FP-receptor selective prostaglandin analogues.

InChI:InChI=1/C15H14O5/c16-8-11-10-6-14(17)19-12(10)7-13(11)20-15(18)9-4-2-1-3-5-9/h1-5,8,10-13H,6-7H2/t10-,11-,12+,13-/m1/s1

Synthetic route

(1S,5R,6S,7R)-7-benzoyloxy-6-hydroxymethyl-2-oxabicyclo[3.3.0]octan-3-one (39746-00-4) → (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5)

Conditions	Yield
With Dess-Martin periodane In dichloromethane at 0 - 20℃; for 1h;	100%
With Dess-Martin periodane In dichloromethane at 0 - 10℃; for 2h;	96.7%
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; trichloroisocyanuric acid; carbonic acid dimethyl ester In ethyl acetate at 0 - 5℃; Inert atmosphere;	95.6%

(1S,5R,6S,7R)-7-benzoyloxy-6-hydroxymethyl-2-oxabicyclo[3.3.0]octan-3-one (39746-00-4) → (1S,5S)-3-oxo-2-oxabicyclo<3.3.0>oct-6-en-6-carbaldehyde (51260-12-9) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5)

Conditions	Yield
With sulfur trioxide pyridine complex Inert atmosphere;

(1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (1S,5S)-3-oxo-2-oxabicyclo<3.3.0>oct-6-en-6-carbaldehyde (51260-12-9)

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at -78℃; for 1h; Elimination;	100%

dimethyl (7-((tert-butyldimethylsilyl)oxy)-2-oxoheptyl)phosphonate (500871-68-1) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (3aR,4R,5R,6aS)-4-(E)-8-(tert-butyldimethylsilyloxy)-3-oxooct-1-enyl-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl benzoate

Conditions	Yield
Stage #1: dimethyl (7-((tert-butyldimethylsilyl)oxy)-2-oxoheptyl)phosphonate With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; for 1h; Inert atmosphere; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In tetrahydrofuran; mineral oil at 0 - 20℃; for 2.5h; Inert atmosphere;	100%

(1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) + ethyl (triphenylphosphoranylidene)acetate (1099-45-2) → Benzoic acid (3aR,4R,5R,6aS)-4-((E)-2-ethoxycarbonyl-vinyl)-2-oxo-hexahydro-cyclopenta[b]furan-5-yl ester (1027275-03-1)

Conditions	Yield
In benzene at 20℃; for 0.5h; Wittig reaction;	98%

1-(triphenylphosphoranylidene)-2-hexanone (41693-11-2) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → C21H24O5

Conditions	Yield
In dichloromethane at 20 - 25℃; for 8h; Wittig Olefination;	97.1%

dimethyl 2-oxoheptylphosphonate (36969-89-8) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (3aR,6aS)-4-((E)-3-Oxo-oct-1-enyl)-3,3a,6,6a-tetrahydro-cyclopenta[b]furan-2-one (49673-16-7) + (3aR,4R,5R,6aS)-benzoic acid 2-oxo-4-[(1E)-3-oxo-oct-1-enyl]-hexahydro-cyclopenta[b]furan-5-yl ester (40834-86-4)

Conditions	Yield
With sodium hexamethyldisilazane In tetrahydrofuran at -78 - 20℃; Horner-Emmons reaction;	A 1% B 96%

2-oxohexylphosphonic acid dimethyl ester (61728-15-2) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (3aR,4R,5R,6aS)-benzoic acid 2-oxo-4-[(1E)-3-oxo-oct-1-enyl]-hexahydro-cyclopenta[b]furan-5-yl ester (40834-86-4)

Conditions	Yield
With sodium hexamethyldisilazane In tetrahydrofuran at -78 - 20℃; Inert atmosphere;	96%

(2,2-difluoro-3-phenoxypropyl) diethyl phosphate + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (3aR,4R,5R,6aS)-4-((E)-3,3-difluoro-4-phenoxybutan-1-en-1-yl)-hexahydro-2-oxo-2H-cyclopenta[b]furan-5-yl benzoate (209861-00-7)

Conditions	Yield
Stage #1: (2,2-difluoro-3-phenoxypropyl) diethyl phosphate With sodium hydride In tetrahydrofuran; mineral oil at 0 - 30℃; for 0.25h; Inert atmosphere; Cooling with ice; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In tetrahydrofuran; mineral oil at 40℃; for 2h;	93.6%

dimethyl 2-oxoheptylphosphonate (36969-89-8) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (3aR,4R,5R,6aS)-benzoic acid 2-oxo-4-[(1E)-3-oxo-oct-1-enyl]-hexahydro-cyclopenta[b]furan-5-yl ester (40834-86-4)

Conditions	Yield
Stage #1: dimethyl 2-oxoheptylphosphonate With lithium hydroxide In tert-butyl methyl ether at 20℃; for 1h; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In tert-butyl methyl ether; water at 20℃; for 1h;	91.5%
Stage #1: dimethyl 2-oxoheptylphosphonate; (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one With lithium chloride In tetrahydrofuran; dichloromethane at -20℃; for 2.5h; Stage #2: With triethylamine In tetrahydrofuran; dichloromethane at -5℃; for 19h;

dimethyl (3-phenoxy-2-oxopropyl)phosphonate (40665-68-7) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (3aR,4R,5R,6aS)-2-oxo-4-((E)-3-oxo-4-phenoxybut-1-en-1-yl)hexahydro-2H-cyclopenta[b]furan-5-yl benzoate (51638-91-6)

Conditions	Yield
With sodium hydride Horner-Emmons reaction;	90%
Stage #1: dimethyl (3-phenoxy-2-oxopropyl)phosphonate With sodium hydride; zinc(II) chloride In tetrahydrofuran; mineral oil at 25 - 35℃; for 0.416667h; Inert atmosphere; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In tetrahydrofuran; dichloromethane; mineral oil at 25 - 40℃; for 2.08333h; Inert atmosphere;	61%
Stage #1: dimethyl (3-phenoxy-2-oxopropyl)phosphonate With sodium hydroxide; zinc(II) chloride In tetrahydrofuran at 27℃; Inert atmosphere; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In tetrahydrofuran at 27℃; for 15h; Inert atmosphere;	50%

4-phenyl-1-(1-phenyl-1H-tetrazole-5-sulfonyl)butan-2-one (1174193-89-5) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (3aR,4R,5R,6aS)-2-oxo-4-((1E)-3-oxo-5-phenylpent-1-en-1-yl)-hexahydro-2H-cyclopenta[b]furan-5-yl benzoate (55076-60-3)

Conditions	Yield
With potassium tert-butylate In dichloromethane; tert-butyl alcohol at -60 - -55℃; Solvent; Inert atmosphere;	89.43%

dimethyl(2-oxo-4-phenylbutyl)phosphonate (41162-19-0) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (3aR,4R,5R,6aS)-2-oxo-4-((1E)-3-oxo-5-phenylpent-1-en-1-yl)-hexahydro-2H-cyclopenta[b]furan-5-yl benzoate (55076-60-3)

Conditions	Yield
Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With N-ethyl-N,N-diisopropylamine; lithium chloride In acetonitrile at -15℃; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In acetonitrile at -15℃; Wittig Reaction;	84.7%
With triethylamine; lithium chloride In tetrahydrofuran; dichloromethane at 0℃; for 2h; Horner-Wadsworth-Emmons Olefination; Cooling with ice;	73%
Stage #1: dimethyl(2-oxo-4-phenylbutyl)phosphonate With sodium hexamethyldisilazane In 1,2-dimethoxyethane Metallation; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In 1,2-dimethoxyethane Condensation;
With n-butyllithium In tetrahydrofuran; hexane; dichloromethane; acetic acid
With triethylamine; lithium chloride In dichloromethane at 0℃; for 2h; Horner-Emmons reaction;

dimethyl diazo-2-oxopropylphosphonate (815610-17-4) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → C16H14O4

Conditions	Yield
With potassium carbonate In methanol at 0 - 5℃; for 12.5h;	81.9%

(1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) + dimethyl (2-oxoheptyl)phosphonate → (3aR,4R,5R,6aS)-benzoic acid 2-oxo-4-[(1E)-3-oxo-oct-1-enyl]-hexahydro-cyclopenta[b]furan-5-yl ester (40834-86-4)

Conditions	Yield
Stage #1: dimethyl (2-oxoheptyl)phosphonate With sodium hydride In tetrahydrofuran at 0 - 20℃; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In tetrahydrofuran at 20℃; for 1.5h;	80%

1-(triphenylphosphoranylidene)-2-heptanone (33803-58-6) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (3aR,4R,5R,6aS)-benzoic acid 2-oxo-4-[(1E)-3-oxo-oct-1-enyl]-hexahydro-cyclopenta[b]furan-5-yl ester (40834-86-4)

Conditions	Yield
at 20 - 30℃; for 8h; Time; Wittig Olefination;	79.2%

(1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) + {2-[(3-methoxymethyl-phenyl)methyl]-2-oxo-ethyl}phosphonic acid dimethyl ester (256382-39-5) → (3aR,4R,5R,6aS)-4-[(1E)-4-[3-(methoxymethyl)phenyl]-3-oxo-1-buten-1-yl]-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl benzoate (1175629-43-2)

Conditions	Yield
Stage #1: {2-[(3-methoxymethyl-phenyl)methyl]-2-oxo-ethyl}phosphonic acid dimethyl ester With sodium hydride In tetrahydrofuran at 20℃; Inert atmosphere; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In tetrahydrofuran for 0.5h; Honer-Emmons reaction; Inert atmosphere;	73.7%

(1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (1S,5R,6S,7R)-7-benzoyloxy-6-hydroxymethyl-2-oxabicyclo[3.3.0]octan-3-one (39746-00-4)

Conditions	Yield
With sodium tetrahydroborate In methanol; dichloromethane at 0℃; for 0.416667h;	69%
With sodium tetrahydroborate In methanol
With sodium tetrahydroborate In methanol; dichloromethane

(1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) + dimethyl [3-(2-iodo-5-trifluoromethyl-phenoxy)-2-oxo-propyl]-phosphonate (336625-17-3) → Benzoic acid (3aR,4R,5R,6aS)-4-[(E)-4-(2-iodo-5-trifluoromethyl-phenoxy)-3-oxo-but-1-enyl]-2-oxo-hexahydro-cyclopenta[b]furan-5-yl ester (336625-19-5)

Conditions	Yield
With triethylamine; lithium chloride In tetrahydrofuran at 5 - 20℃; for 3.33333h;	60%

C15H27(2)H6O5PSi (1352751-86-0) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → C28H34(2)H6O6Si

Conditions	Yield
With triethylamine In tetrahydrofuran at -10 - 20℃; Inert atmosphere;	54%

Methyltriphenylphosphonium bromide (1779-49-3) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (1S,5R,6R,7R)-7-(benzoyloxy)-6-vinyl-2-oxabicyclo[3.3.0]octan-3-one (618387-07-8)

Conditions	Yield
Stage #1: Methyltriphenylphosphonium bromide With sodium hexamethyldisilazane In tetrahydrofuran at -30℃; for 0.5h; Inert atmosphere; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere;	51%
With potassium tert-butylate In tetrahydrofuran Wittig olefination;

dimethyl 4-(3-trifluoromethylphenyl)-2-oxobutylphosphonate (70783-99-2) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → Benzoic acid (3aR,4R,5R,6aS)-2-oxo-4-[(E)-3-oxo-5-(3-trifluoromethyl-phenyl)-pent-1-enyl]-hexahydro-cyclopenta[b]furan-5-yl ester (294856-03-4)

Conditions	Yield
Stage #1: dimethyl 4-(3-trifluoromethylphenyl)-2-oxobutylphosphonate With sodium hexamethyldisilazane In 1,2-dimethoxyethane Metallation; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In 1,2-dimethoxyethane Condensation;	50%

dimethyl (3,3-difluoro-2-oxoheptyl)-phosphonate (50889-46-8) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (3aR,4R,5R,6aS)-4-((E)-4,4-difluoro-3-oxooct-1-enyl)-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl benzoate

Conditions	Yield
Stage #1: dimethyl (3,3-difluoro-2-oxoheptyl)-phosphonate With lithium hydroxide In tert-butyl methyl ether at 20℃; for 1h; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In tert-butyl methyl ether; water at 20℃; for 3h; Product distribution / selectivity;	49.5%
Stage #1: dimethyl (3,3-difluoro-2-oxoheptyl)-phosphonate With lithium hydride In tert-butyl methyl ether at 20℃; for 2h; Stage #2: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In tert-butyl methyl ether at 20℃; for 6h; Product distribution / selectivity;	4.8%
Stage #1: dimethyl (3,3-difluoro-2-oxoheptyl)-phosphonate With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.5h; Inert atmosphere; Stage #2: With zinc(II) chloride In tetrahydrofuran; mineral oil at 26℃; for 0.5h; Inert atmosphere; Stage #3: (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one In tetrahydrofuran; mineral oil at 25 - 45℃; for 20h;

dimethyl 2-oxoheptylphosphonate (36969-89-8) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (3aR,4R,5R,6aS)-benzoic acid 2-oxo-4-[(1E)-3-oxo-oct-1-enyl]-hexahydro-cyclopenta[b]furan-5-yl ester (40834-86-4) + Benzoic acid (3aR,4R,5R,6aS)-2-oxo-4-((Z)-3-oxo-oct-1-enyl)-hexahydro-cyclopenta[b]furan-5-yl ester

Conditions	Yield
With lithium hexamethyldisilazane In tetrahydrofuran at -78 - 20℃; Horner-Emmons reaction;	A n/a B 20%

diazomethane (186581-53-3, 908094-01-9) + methyl 2,2,5-trimethylhex-4-enoate (66478-19-1) + (4-carboxybutyl)triphenylphosphonium bromide (17814-85-6) + Methyltriphenylphosphonium bromide (1779-49-3) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (5Z.10Z.13E)-(8R.12R.15S)-15-Hydroxy-9-oxo-16.16.19-trimethyl-5.10.13.18-prostatetraensaeure-methylester

Conditions	Yield
Multistep reaction;

diazomethane (186581-53-3, 908094-01-9) + methyl 5-methyl-hex-4-enoate (35901-76-9) + (4-carboxybutyl)triphenylphosphonium bromide (17814-85-6) + methyllithium (917-54-4) + Methyltriphenylphosphonium bromide (1779-49-3) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (5Z.13E)-(8R.11R.12R.15R)-15-Hydroxy-9-oxo-11.19-dimethyl-5.13.18-prostatriensaeure-methylester

Conditions	Yield
Multistep reaction;

diazomethane (186581-53-3, 908094-01-9) + methyl 5-methyl-hex-4-enoate (35901-76-9) + (4-carboxybutyl)triphenylphosphonium bromide (17814-85-6) + methyllithium (917-54-4) + Methyltriphenylphosphonium bromide (1779-49-3) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (5Z.13E)-(8R.11R.12R.15S)-15-Hydroxy-9-oxo-11.19-dimethyl-5.13.18-prostatriensaeure-methylester

Conditions	Yield
Multistep reaction;

diazomethane (186581-53-3, 908094-01-9) + methyl 5-methyl-hex-4-enoate (35901-76-9) + methylmagnesium bromide (75-16-1) + (4-carboxybutyl)triphenylphosphonium bromide (17814-85-6) + Methyltriphenylphosphonium bromide (1779-49-3) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (5Z.10Z.13E)-(8R.12R.15RS)-15-Hydroxy-9-oxo-15.19-dimethyl-5.10.13.18-prostatetraensaeure-methylester

Conditions	Yield
Multistep reaction;

diazomethane (186581-53-3, 908094-01-9) + methyl 5-methyl-hex-4-enoate (35901-76-9) + (4-carboxybutyl)triphenylphosphonium bromide (17814-85-6) + Methyltriphenylphosphonium bromide (1779-49-3) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (5Z.13E)-(8R.11R.12R.15S)-9-Oxo-11.15-dihydroxy-19-methyl-5.13.18-prostatriensaeuremethylester (66477-71-2)

Conditions	Yield
Multistep reaction;

diazomethane (186581-53-3, 908094-01-9) + methyl 5-methyl-hex-4-enoate (35901-76-9) + (4-carboxybutyl)triphenylphosphonium bromide (17814-85-6) + Methyltriphenylphosphonium bromide (1779-49-3) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (8R.9S.11R.12R.15R)-9.11.15-Trihydroxy-19-methyl-18-prostensaeuremethylester (66477-98-3)

Conditions	Yield
Multistep reaction;

diazomethane (186581-53-3, 908094-01-9) + methyl 5-methyl-hex-4-enoate (35901-76-9) + (4-carboxybutyl)triphenylphosphonium bromide (17814-85-6) + Methyltriphenylphosphonium bromide (1779-49-3) + (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicyclo[3.3.0]octan-3-one (39746-01-5) → (5Z.13E)-(8R.12R.15S)-15-Hydroxy-9-oxo-19-methyl-5.13.18-prostatriensaeure-methylester (66477-82-5)

Conditions	Yield
Multistep reaction;

Upstream product

• 39746-00-4 (1S,5R,6S,7R)-7-benzoyloxy-6-hydroxymethyl-2-oxabicyclo[3.3.0]octan-3-one 
• 172821-93-1 C₁₅H₁₆O₅ 

Downstream Products

• 110828-48-3 Benzoic acid (3aR,4R,5R,6aS)-4-{(E)-5-[2-(tert-butyl-dimethyl-silanyloxy)-4-(trityl-amino)-phenyl]-3-oxo-pent-1-enyl}-2-oxo-hexahydro-cyclopenta[b]furan-5-yl ester 
• 1027275-03-1 Benzoic acid (3aR,4R,5R,6aS)-4-((E)-2-ethoxycarbonyl-vinyl)-2-oxo-hexahydro-cyclopenta[b]furan-5-yl ester 
• 170290-67-2 (3aR,4R,5R,6aS)-5-(Benzoyloxy)4-[(E)-3-cyclohexyl-3-oxo-1-propenyl]-hexahydro-2H-cyclopenta[b]furan-2-one 
• 55076-60-3 (3aR,4R,5R,6aS)-2-oxo-4-((1E)-3-oxo-5-phenylpent-1-en-1-yl)-hexahydro-2H-cyclopenta[b]furan-5-yl benzoate 
• 294856-03-4 Benzoic acid (3aR,4R,5R,6aS)-2-oxo-4-[(E)-3-oxo-5-(3-trifluoromethyl-phenyl)-pent-1-enyl]-hexahydro-cyclopenta[b]furan-5-yl ester 
• 40834-86-4 (3aR,4R,5R,6aS)-benzoic acid 2-oxo-4-[(1E)-3-oxo-oct-1-enyl]-hexahydro-cyclopenta[b]furan-5-yl ester 
• 51638-91-6 (3aR,4R,5R,6aS)-2-oxo-4-((E)-3-oxo-4-phenoxybut-1-en-1-yl)hexahydro-2H-cyclopenta[b]furan-5-yl benzoate 
• 120962-75-6 [3aR,4R(1E,3S),5R,6aS]-4-[3-cyclohexyl-3-(tetrahydropyran-2-yloxy)-1-propenyl]-5-(tetrahydropyran-2-yloxy)hexahydro-2H-cyclopenta[b]furan-2-one 

Relevant articles and documents

Preparation method of carboprost tromethamine intermediate

The invention provides a preparation method of a carboprost tromethamine intermediate. The method comprises the following steps: A) carrying out an oxidation reaction on benzoyl corey lactone alcohol shown in a formula I under the action of a catalyst and an oxidizing agent to obtain benzoyl corey lactone aldehyde shown in a formula II; B) reacting the benzoyl corey lactone aldehyde as shown in the formula II with dimethyl (2-oxoheptyl) phosphonate under the action of alkali to obtain a 15-ketone crude product as shown in a formula III, and recrystallizing the 15-ketone crude product to obtain a 15-ketone pure product; and C) carrying out methylation reaction on the 15-ketone pure product to obtain the carboprost tromethamine intermediate as shown in a formula IV. According to the invention, the use of reagents with high toxicity and serious environmental pollution is avoided; when the carboprost intermediate 15-ketone is prepared, a mixed solvent is adopted for recrystallization, so that column chromatography is omitted, operation is easy and convenient, reagents are saved, and cost is reduced; and in the methylate preparation process, ultralow temperature is avoided, and the reaction time is shortened, so that the energy consumption is reduced, and the purity and the yield are relatively high.

Carboprost tromethamine related impurity L-amyl 15-ketone and preparation method thereof

The invention relates to a carboprost tromethamine related impurity L-amyl 15-ketone and a preparation method thereof. The preparation method comprises the following steps of: (1) in the presence of afifth organic solvent, carrying out dehydrogenation reaction on methyl triphenyl phosphine halide by using strong base, adding ethyl valerate after reaction for a certain time, continuously reactingfor a certain time to obtain 1-triphenylphosphine 2-hexanone; and (2) carrying out wittig reaction on the 1-triphenylphosphine 2-hexanone obtained in the step (1) and a second organic solvent solutionof benzoyl corey lactone aldehyde to obtain a pentyl-15 ketone crude product. The method has the advantages of simple and convenient operation, high safety, and high yield and purity of an obtained product under optimal conditions, and can meet the requirements for impurity research.

15-ketone preparation method

The present invention relates to a drug intermediate 15-ketone preparation method in chemical field. The preparation method comprises the following steps: (1) (-)-Corey lactone benzoate, an oxidizing agent and a catalyst are added into a first organic solvent for oxidation to obtain a reaction solution A; (2) after a dilute acid is dropwise added into the reaction solution A obtained in the step (1), the solution is stirred and filtered, the filtrate is extracted directly with the first organic solvent, an organic phase is washed with water, dehydrated with a desiccant and filtered to obtain a (-)-Corey lactone benzoate aldehyde solution; (3) Wittig reagent is added into the (-)-Corey lactone benzoate aldehyde solution obtained in the step (2) for Wittig reaction to obtain a reaction solution B, the reaction solution B is concentrated, a second organic solvent is added, and after cooling and crystallization, a crystallization liquid is obtained; and (4) the crystallization liquid obtained in the step (3) is filtered, the filter cake is washed with a third organic solvent, the filter cake is dissolved by the first organic solvent for impurity removal, and after filteration and concentration, an oil matter is obtained. The drug intermediate 15-ketone preparation method has the advantages of good product quality and the like.