709031-28-7

Usage

Uses

Used in Pharmaceutical Industry:
3-Hydroxy-α-oxoadamantane-1-acetic acid is used as a reactant/reagent for the preparation method of saxagliptin intermediate (S)-N-tert-butoxycarbonyl-3-hydroxy-1-adamantyl-D-glycine. This is achieved through enzymic synthesis in the presence of aminotransferase, which is a crucial step in the production of saxagliptin, a medication used to treat type 2 diabetes.

InChI:InChI=1/C12H16O4/c13-9(10(14)15)11-2-7-1-8(3-11)5-12(16,4-7)6-11/h7-8,16H,1-6H2,(H,14,15)

Synthetic route

dichloro-(3-hydroxy-adamantan-1-yl)-acetic acid methyl ester (709031-35-6) → 3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7)

Conditions	Yield
Stage #1: dichloro-(3-hydroxy-adamantan-1-yl)-acetic acid methyl ester With sodium hydroxide In tetrahydrofuran; water at 20℃; for 16.7h; Stage #2: With hydrogenchloride; sodium hydrogencarbonate In tetrahydrofuran; water for 5h; pH=7.4; Heating;	99.53%
Stage #1: dichloro-(3-hydroxy-adamantan-1-yl)-acetic acid methyl ester With sodium hydroxide In tetrahydrofuran; water at 20℃; for 16h; pH=13.24; Stage #2: With hydrogenchloride; sodium hydrogencarbonate In tetrahydrofuran; water at 4 - 20℃; for 101.76h; pH=1.4 - 1.77;	86.6%

dichloro-(3-hydroxy-adamantan-1-yl)-acetic → 3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7)

Conditions	Yield
Stage #1: dichloro-(3-hydroxy-adamantan-1-yl)-acetic With sodium hydroxide; sodium hydrogencarbonate In water at 80℃; for 6h; pH=7.22; Stage #2: With hydrogenchloride In water pH=0.15;	99%

1-hydroxy-3-acetyladamantane (39917-38-9) → 3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7)

Conditions	Yield
With potassium permanganate; tetrabutylammomium bromide; potassium hydroxide In tert-butyl alcohol at 40℃; for 5h; Reagent/catalyst;	91.8%
With potassium permanganate; potassium hydroxide In tert-butyl alcohol at 40℃; for 5h;	90%
With potassium permanganate; potassium hydroxide In water; tert-butyl alcohol at 35 - 45℃; for 4.5h;	86.6%

3-hydroxy-α-oxotricyclo[3.3.1.13,7]decane-1-acetic acid methyl ester → 3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7)

Conditions	Yield
Stage #1: 3-hydroxy-α-oxotricyclo[3.3.1.13,7]decane-1-acetic acid methyl ester With sodium hydroxide; water In tetrahydrofuran at 5 - 30℃; for 0.5h; pH=7 - 14; Stage #2: With hydrogenchloride In tetrahydrofuran; water; ethyl acetate pH=0.7;	85%
With sodium hydroxide In tetrahydrofuran; water at 30℃; pH=Ca. 7 - 14; Cooling with ice;

1-acetyladamantane (1660-04-4) → 3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7)

Conditions	Yield
With potassium permanganate; potassium hydroxide In water at 90℃;	84%
With potassium permanganate; N-benzyl-N,N,N-triethylammonium chloride; sodium hydroxide at 60 - 80℃; for 14.5h;	47%
Stage #1: 1-acetyladamantane With sodium hydroxide; potassium permanganate In water at 27 - 55℃; for 24.5 - 25.5h; Stage #2: In water Product distribution / selectivity; Acidic aqueous solution;

1-acetyladamantane (1660-04-4) → 3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7) + oxo-tricyclo[3.3.1.13,7]decan-1-yl-acetic acid (16091-98-8)

Conditions	Yield
With potassium permanganate; potassium hydroxide In water at 50 - 80℃; for 12h;	A 80% B 0.8 g
With sodium hydroxide; potassium permanganate In water; tert-butyl alcohol at 50 - 65℃; for 35h; Product distribution / selectivity;

oxo-tricyclo[3.3.1.13,7]decan-1-yl-acetic acid (16091-98-8) → 3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7)

Conditions	Yield
Stage #1: oxo-tricyclo[3.3.1.13,7]decan-1-yl-acetic acid With sulfuric acid; nitric acid Stage #2: With hydrogenchloride In water	76%
Stage #1: oxo-tricyclo[3.3.1.13,7]decan-1-yl-acetic acid With sodium hydroxide; potassium permanganate In water at 20 - 60℃; for 11h; Stage #2: Acidic aqueous solution;
With sodium hydroxide; potassium permanganate In water at 55 - 60℃; for 11h; Product distribution / selectivity;

3-hydroxy-1-adamantyl-glycine → 3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7)

Conditions	Yield
With ω-transaminase

1-Adamantanecarboxylic acid (828-51-3) → 3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 1,1'-carbonyldiimidazole / dichloromethane / 0.5 h / 25 °C 1.2: 2 h / 25 °C 2.1: tetrahydrofuran / 10 - 20 °C / Inert atmosphere 3.1: potassium permanganate; potassium hydroxide / water / 90 °C View Scheme
Multi-step reaction with 4 steps 1.1: potassium permanganate; potassium hydroxide / water; tert-butyl alcohol / 8.5 h / 45 - 60 °C 2.1: thionyl chloride / 6 h / Reflux 3.1: sodium / Petroleum ether / 20 °C 3.2: 20 °C / Reflux 3.3: 6 h / Reflux 4.1: potassium permanganate; potassium hydroxide / tert-butyl alcohol / 5 h / 40 °C View Scheme

1-Adamantanecarboxylic acid (828-51-3) → 3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7) + oxo-tricyclo[3.3.1.13,7]decan-1-yl-acetic acid (16091-98-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 1,1'-carbonyldiimidazole / dichloromethane / 0.5 h / 25 °C 1.2: 2 h / 25 °C 2.1: tetrahydrofuran / 10 - 20 °C / Inert atmosphere 3.1: potassium permanganate; potassium hydroxide / water / 12 h / 50 - 80 °C View Scheme

(3r,5r,7r)-N-methoxy-N-methyladamantane-1-carboxamide (351464-84-1) → 3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7) + oxo-tricyclo[3.3.1.13,7]decan-1-yl-acetic acid (16091-98-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: tetrahydrofuran / 10 - 20 °C / Inert atmosphere 2: potassium permanganate; potassium hydroxide / water / 12 h / 50 - 80 °C View Scheme

1-acetyl-3-chloroadamantane (143467-20-3) → 3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium hydroxide / water / 6 h / Reflux 2: potassium hydroxide; potassium permanganate / water; tert-butyl alcohol / 4.5 h / 35 - 45 °C View Scheme

1-Adamantyl bromide (768-90-1) → 3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: zinc(II) chloride / dichloromethane / 20 °C 2.1: sulfuric acid; nitric acid / water / 25 h / 1 °C / Cooling with ice 3.1: sodium hydroxide / water; tetrahydrofuran / 16.7 h / 20 °C 3.2: 5 h / pH 7.4 / Heating View Scheme
Multi-step reaction with 5 steps 1: zinc(II) chloride / dichloromethane / 0.08 h / 20 °C / Large scale 2: acetyl chloride / 2 h / 0 - 25 °C / Inert atmosphere; Large scale 3: oxalyl dichloride / dichloromethane; dimethyl sulfoxide / 0.83 h / -60 °C / Inert atmosphere; Cooling with acetone-dry ice 4: sulfuric acid; nitric acid / water / Cooling with ice 5: sodium hydroxide / water; tetrahydrofuran / 30 °C / pH Ca. 7 - 14 / Cooling with ice View Scheme

α-oxotricyclo[3.3.1.13,7]decane-1-acetic acid methyl ester → 3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: sulfuric acid; nitric acid / water / Cooling with ice 2: sodium hydroxide / water; tetrahydrofuran / 30 °C / pH Ca. 7 - 14 / Cooling with ice View Scheme

dichloro-(tricyclo[3.3.1.13,7]decan-1-yl)acetic acid methyl ester (709031-34-5) → 3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sulfuric acid; nitric acid / water / 25 h / 1 °C / Cooling with ice 2.1: sodium hydroxide / water; tetrahydrofuran / 16.7 h / 20 °C 2.2: 5 h / pH 7.4 / Heating View Scheme

α-hydroxytricyclo[3.3.1.13,7]decane-1-acetic acid methyl ester (128665-98-5) → 3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: oxalyl dichloride / dichloromethane; dimethyl sulfoxide / 0.83 h / -60 °C / Inert atmosphere; Cooling with acetone-dry ice 2: sulfuric acid; nitric acid / water / Cooling with ice 3: sodium hydroxide / water; tetrahydrofuran / 30 °C / pH Ca. 7 - 14 / Cooling with ice View Scheme

α-hydroxytricyclo[3.3.1.13,7]decane-1-acetic acid (30074-09-0) → 3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: acetyl chloride / 2 h / 0 - 25 °C / Inert atmosphere; Large scale 2: oxalyl dichloride / dichloromethane; dimethyl sulfoxide / 0.83 h / -60 °C / Inert atmosphere; Cooling with acetone-dry ice 3: sulfuric acid; nitric acid / water / Cooling with ice 4: sodium hydroxide / water; tetrahydrofuran / 30 °C / pH Ca. 7 - 14 / Cooling with ice View Scheme

3-hydroxy-1-adamantanecarbonyl chloride → 3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium / Petroleum ether / 20 °C 1.2: 20 °C / Reflux 1.3: 6 h / Reflux 2.1: potassium permanganate; potassium hydroxide / tert-butyl alcohol / 5 h / 40 °C View Scheme

3-hydroxyadamantane-1-carboxylic acid (42711-75-1) → 3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: thionyl chloride / 6 h / Reflux 2.1: sodium / Petroleum ether / 20 °C 2.2: 20 °C / Reflux 2.3: 6 h / Reflux 3.1: potassium permanganate; potassium hydroxide / tert-butyl alcohol / 5 h / 40 °C View Scheme

3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7) → (αS)-α-amino-3-hydroxytricyclo[3.3.1.13,7]decane-1-acetic acid

Conditions	Yield
With NAD; ammonium formate; diothiothreitol In ammonium hydroxide at 40℃; for 38h; pH=8.0; Enzymatic reaction;	100%
With glutamate at 37℃; for 0.5h; pH=8; Kinetics; Reagent/catalyst; aq. phosphate buffer; Enzymatic reaction; optical yield given as %ee;	100%
With 4-aminomethylphenol; Na(1+)*C20H23N2O4S(1-); sodium hydroxide In water at 40℃; for 12h; Reagent/catalyst; Temperature; enantioselective reaction;	98.2%

3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7) + ethanol (64-17-5) → 2-(3-hydroxy-1-adamantyl)-2-oxoacetic acid ethyl ester

Conditions	Yield
With acetyl chloride at 5℃; for 3h; Inert atmosphere; Reflux;	95%
With thionyl chloride at 0 - 5℃; for 1h; Inert atmosphere;	90%

3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7) + isopropyl alcohol (67-63-0) → 2-(3-hydroxy-1-adamantyl)-2-oxo acetic acid isopropyl ester

Conditions	Yield
With thionyl chloride at 0 - 5℃; for 1h; Inert atmosphere;	95%
With acetyl chloride at 5℃; for 3h; Inert atmosphere; Reflux;	80%

methanol (67-56-1) + 3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7) → 3-hydroxy-α-oxotricyclo[3.3.1.13,7]decane-1-acetic acid methyl ester

Conditions	Yield
With acetyl chloride at 5℃; for 3h; Inert atmosphere; Reflux;	93%

3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7) → 2-(3-hydroxy-1-adamantyl)-2-hydroxyiminoacetic acid

Conditions	Yield
With hydroxylamine hydrochloride; sodium hydroxide In water at 0 - 5℃; for 2h; pH=7;	90%
With hydroxylamine hydrochloride; sodium hydroxide In water for 4h; Cooling with ice;	90%

3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7) → 3-hydroxy-1-adamantyl-glycine

Conditions	Yield
With ammonium formate; dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer In methanol at 50℃; for 24h; Inert atmosphere;	86%
With α-transaminase

3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7) + 2-methyl-propan-1-ol (78-83-1) → C16H24O4

Conditions	Yield
With thionyl chloride at 0 - 5℃; for 1h;	80%

3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7) + isobutene (115-11-7) → tert-butyl 2-(3-hydroxy-1-adamantyl)-2-oxoacetate

Conditions	Yield
With sulfuric acid In 1,4-dioxane; dichloromethane at -30 - 20℃; for 20h; Sealed tube; High pressure;	75%

3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7) + rac-methylbenzylamine (618-36-0) → (αS)-α-amino-3-hydroxytricyclo[3.3.1.13,7]decane-1-acetic acid + acetophenone (98-86-2)

Conditions	Yield
With L-2-aminobutyric acid; pyridoxal 5'-phosphate; (S)-selective ω-transaminase from Paracoccus denitrificans; branched-chain aminoacid transaminase In aq. phosphate buffer; hexane at 37℃; for 61h; pH=7; Reagent/catalyst; Enzymatic reaction; enantioselective reaction;	A 62% B n/a

3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7) + (1S,3S,5S)-2-azabicyclo[3.1.0]hexane-3-carboxamide → (1S,3S,5S)-2-(2-(3-hydroxyadamantan-1-yl)-2-oxoacetyl)-2-azabicyclo[3.1.0]hexan-3-carboxamide

Conditions	Yield
With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine In acetonitrile at -5 - 15℃; for 1.5h;	4.38 g

3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7) → (1S,3S,5S)-2-(2-(3-hydroxyadamantan-1-yl)-2-(hydroxyimino)acetyl)-2-azabicyclo[3.1.0]hexan-3-carboxamide

Conditions	Yield
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / acetonitrile / 1.5 h / -5 - 15 °C 2: hydroxylamine hydrochloride; sodium acetate / water; methanol / 23 h / 40 °C View Scheme

3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7) → (1S,3S,5S)-2-(2-(3-hydroxyadamantan-1-yl)-2-(hydroxyimino)acetyl)-2-azabicyclo[3.1.0]hexan-3-carbonitrile

Conditions	Yield
Multi-step reaction with 3 steps 1.1: N-ethyl-N,N-diisopropylamine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / acetonitrile / 1.5 h / -5 - 15 °C 2.1: 3-pyridinecarboxylic acid ethyl ester; trifluoroacetic anhydride / ethyl acetate / 1 h / 0 °C 2.2: 10 - 15 °C 3.1: hydroxylamine hydrochloride / water; methanol / 40 °C View Scheme

3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7) → (1S,3S,5S)-2-((S)-2-amino-2-(3-hydroxyadamantan-1-yl)acetyl)-2-azabicyclo[3.1.0]hexan-3-carboxamide

Conditions	Yield
Multi-step reaction with 3 steps 1: N-ethyl-N,N-diisopropylamine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / acetonitrile / 1.5 h / -5 - 15 °C 2: hydroxylamine hydrochloride; sodium acetate / water; methanol / 23 h / 40 °C 3: hydrogen / methanol View Scheme

3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7) → saxagliptin

Conditions	Yield
Multi-step reaction with 3 steps 1.1: N-ethyl-N,N-diisopropylamine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / acetonitrile / 1.5 h / -5 - 15 °C 2.1: 3-pyridinecarboxylic acid ethyl ester; trifluoroacetic anhydride / ethyl acetate / 1 h / 0 °C 2.2: 10 - 15 °C 3.1: pyridoxamine dihydrochloride; potassium carbonate; cinchonidine / water; methanol / 48 h / 50 °C View Scheme
Multi-step reaction with 6 steps 1.1: pyrographite / water / 0.08 h / pH Ca. 8 / Large scale 1.2: 42 h / 40 °C / pH 7.5 - 8 / Large scale 2.1: sodium hydroxide / Isopropyl acetate / 4 h / 20 °C / pH 10 / Large scale 3.1: methanesulfonyl chloride; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / Cooling with acetone-dry ice 3.2: 20 °C 4.1: pyridine; trifluoroacetic anhydride / 0.5 h / Cooling with ice 4.2: 7.55 h / Cooling 5.1: dichloromethane / methanol / 20 °C / Inert atmosphere 6.1: water; dichloromethane View Scheme

3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7) → (1S,3S,5S)-2-(2-(3-hydroxyadamantan-1-yl)-2-oxoacetyl)-2-azabicyclo[3.1.0]hexan-3-carbonitrile

Conditions	Yield
Multi-step reaction with 2 steps 1.1: N-ethyl-N,N-diisopropylamine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / acetonitrile / 1.5 h / -5 - 15 °C 2.1: 3-pyridinecarboxylic acid ethyl ester; trifluoroacetic anhydride / ethyl acetate / 1 h / 0 °C 2.2: 10 - 15 °C View Scheme

3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7) → C13H21NO3

Conditions	Yield
Multi-step reaction with 2 steps 1: acetyl chloride / 3 h / 5 °C / Inert atmosphere; Reflux 2: palladium 10% on activated carbon; ammonium formate / ethanol / 40 °C / 4560.31 Torr / Inert atmosphere View Scheme

3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7) → C14H23NO3

Conditions	Yield
Multi-step reaction with 2 steps 1: acetyl chloride / 3 h / 5 °C / Inert atmosphere; Reflux 2: palladium 10% on activated carbon; ammonium formate / ethanol / 40 °C / 4560.31 Torr / Inert atmosphere View Scheme

3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7) → isopropyl 2-amino-2-(3-hydroxy-1-adamantyl)acetate

Conditions	Yield
Multi-step reaction with 2 steps 1: acetyl chloride / 3 h / 5 °C / Inert atmosphere; Reflux 2: palladium 10% on activated carbon; ammonium formate / ethanol / 40 °C / 4560.31 Torr / Inert atmosphere View Scheme

3-hydroxy-α-oxotricyclo [3.3.1.13,7]decane-1-acetic acid (709031-28-7) → C16H27NO3

Conditions	Yield
Multi-step reaction with 2 steps 1: sulfuric acid / 1,4-dioxane; dichloromethane / 20 h / -30 - 20 °C / Sealed tube; High pressure 2: palladium 10% on activated carbon; ammonium formate / ethanol / 40 °C / 4560.31 Torr / Inert atmosphere View Scheme

Upstream product

• 1660-04-4 1-acetyladamantane 
• 709031-29-8 3-hydroxy-1-adamantyl-glycine 
• 42711-75-1 3-hydroxyadamantane-1-carboxylic acid 
• 30074-09-0 α-hydroxytricyclo[3.3.1.13,7]decane-1-acetic acid 
• 128665-98-5 α-hydroxytricyclo[3.3.1.1^3,7]decane-1-acetic acid methyl ester 
• 709031-34-5 dichloro-(tricyclo[3.3.1.1^3,7]decan-1-yl)acetic acid methyl ester 
• 768-90-1 1-Adamantyl bromide 
• 143467-20-3 1-acetyl-3-chloroadamantane 
• 351464-84-1 (3r,5r,7r)-N-methoxy-N-methyladamantane-1-carboxamide 
• 828-51-3 1-Adamantanecarboxylic acid 
• 16091-98-8 oxo-tricyclo[3.3.1.1^3,7]decan-1-yl-acetic acid 
• 39917-38-9 1-hydroxy-3-acetyladamantane 
• 709031-35-6 dichloro-(3-hydroxy-adamantan-1-yl)-acetic acid methyl ester 

Downstream Products

• 361442-00-4 (αS)-α-[[(1,1-dimethylethoxy)carbonyl]-amino]-3-hydroxytricyclo[3.3.1.1^3,7]decane-1-acetic acid 
• 709031-43-6 3-cyano-(αS)-α-(3-hydroxytricyclo[3.3.1.1^3,7]dec-1-yl)-β-oxo-(1S,3S,5S)-2-azabicyclo[3.1.0]hexane-2-ethanecarbamic acid 1,1-dimethylethyl ester 
• 709031-78-7 Saxagliptin hydrochloride 
• 361442-01-5 tert-butyl [(1S)-2-[(1S,3S,5S)-3-carbamoyl-2-azabicyclo[3.1.0]hex-2-yl]-1-(3-hydroxytricyclo[3.3.1.1³'⁷]dec-1-yl)-2-oxoethyl]carbamate 
• 709031-29-8 (αS)-α-amino-3-hydroxytricyclo[3.3.1.1^3,7]decane-1-acetic acid 
• 98-86-2 acetophenone 
• 1564265-93-5 saxagliptin 
• 709031-29-8 3-hydroxy-1-adamantyl-glycine 

Relevant academic research and scientific papers

Method for preparing non-natural amino acid

The invention relates to a preparation and chiral resolution method for unnatural amino acids. The method comprises the following steps: with adamantanecarboxylic acid as a raw material, preparing 3-hydroxy-adamantanecarboxylic acid; carrying out chlorination, oxidation and the like so as to obtain 2-(3-hydroxy-1-adamantyl)glyoxalic acid; reacting 2-(3-hydroxy-1-adamantyl)glyoxalic acid with hydroxylamine hydrochloride so as to obtain 3-hydroxyadamantyl-glyoxalic acid oxime; carrying out reduction with a reducing agent and protection with Boc acid anhydride so as to obtain N-tertbutyloxycarbonyl-3-hydroxyadamantylglycine; and carrying out resolution with organic base so as to obtain two unnatural amino acids, i.e., (S)-N-tertbutyloxycarbonyl-3-hydroxyadamantylglycine and (R)-N-tertbutyloxycarbonyl-3-hydroxyadamantylglycine. Compared with the prior art, the method provided by the invention has the following advantages: improved synthesis technology; mild reaction conditions; small environmental pollution; and applicability to industrial production.

An Efficient and Practical Method for the Synthesis of Saxagliptin Intermediate 2-(3-Hydroxy-1-adamantane)-2-oxoacetic Acid and Its Optimization

A mild and relatively simple way for preparation of 2-(3-hydroxy-1-adamantane)-2-oxoacetic acid (I) was reported. It was prepared from 1-adamantanecarboxylic acid (II) via sulfuric acid/nitric acid to get 3-hydroxy-1-adamantanecarboxylic acid (III); treated with the one-pot method through acylation, condensation, and decarboxylation to obtain 3-hydroxy-1-acetyladamantane (IV); and finally oxidized by potassium permanganate (KMnO4) to get the target compound (I). The overall yield was about 60%, which provides a new idea for commercial production of saxagliptin intermediate.

A facile and economic method for the synthesis of (S)-N-Boc-3′-hydroxyadamantylglycine

(S)-N-Boc-3′-hydroxyadamantylglycine (I) is an important intermediate of saxagliptin for type 2 diabetes mellitus (T2DM). It was prepared from 1-adamantanecarboxylic acid(1) via mild reaction with sulfuric acid/nitric acid, VHA reagent (SOCl2/DMF) and sodium diethyl malonate, then was treated with hydrolysis, decarboxylation, alkalization and oxidation to give 2-(3-hydroxy-1-adamantyl)-2-oxoacetic acid (4), then through oximation, reduction and (Boc)2O protection to give the N-Boc-3′-hydroxyadamantylglycine(6), then was treated with quinidine to get (S)- N-Boc-3′-hydroxyadamantylglycine(I) and quinine to get (R)–N-Boc-3′-hydroxyadamantylglycine(II). Finally, Compound II was racemized by dicyclohexylcarbodiimide (DCC) and sodium?hydride (NaH) to afford compound 6. In this route, the overall yield of preparing compound I was about 35?% and the enantiomeric excess (ee) reach to 99?%. This route provided a novel idea for the preparation of (S)-N-Boc-3′-hydroxyadamantylglycine.

PROCESS FOR PREPARING DIPEPTIDYL PEPTIDASE IV INHIBITORS AND INTERMEDIATES THEREFOR

A process for preparing an amine of the structure which comprises a. treating an aqueous solution of a keto acid of the structure with ammonium formate, nicotinamide adenine dinucleotide, dithiothreitol and partially purified phenylalanine dehydrogenase and/or formate dehydrogenase enzyme (PDH/FDH); and b. adjusting pH of the reaction mixture with sodium hydroxide to form the desired amine which is substantially free of undesirable excess ammonium ions.

Preparation method of saxagliptin intermediate (A1)

The invention discloses a preparation method of a saxagliptin intermediate (A1), and belongs to the field of chemical pharmacy. Adamantyloxoacetic acid is obtained through a Grignard reaction, hydrolysis and a mixed acid reaction with bromoadamantane as an initial raw material. The method has the advantages of simple and easy operation, high yield, small pollution, and suitableness for industrial production.

A novel method for the synthesis of 2-(3-hydroxy-1-adamantyl)-2-oxoacetic acid

A simple and efficient synthetic route to 2-(3-hydroxy-1-adamantyl)-2- oxoacetic acid is described by a direct oxidation reaction of adamantan-1-yl-ethan-1-one which could be prepared by a Grignard reaction. In this approach, the oxidation reaction introduced the hydroxyl and carboxyl group by a one-pot reaction.

Biocatalytic asymmetric synthesis of unnatural amino acids through the cascade transfer of amino groups from primary amines onto keto acids

Flee to the hills: An unfavorable equilibrium in the amino group transfer between amino acids and keto acids catalyzed by α-transaminases was successfully overcome by coupling with a ω-transaminase reaction as an equilibrium shifter, leading to efficient asymmetric synthesis of diverse unnatural amino acids, including L-tert-leucine and D-phenylglycine. Copyright

Preparation of 2-(3-hydroxy-1-adamantyl)-2-oxoacetic acid: A key intermediate for saxagliptin

An optimized synthetic approach to prepare 2-(3-hydroxy-1-adamantyl)-2- oxoacetic acid has been reported in a good yield under mild experimental conditions. It was synthesized from 1-adamantanecarboxylic acid via successful reaction with thionyl chloride and sodium diethyl malonate to give dimethyl (1-adamantylcarbonyl) malonate, which was subjected to hydrolysis and decarboxylation by a mixture of acetic acid with water and sulfuric acid and then oxidation by potassium permanganate. The synthesized adamantane derivative was utilized to saxagliptin.

Process for the preparation of adamantane derivatives

The invention relates to a process for the preparation of 3-hydroxyadamantaneglyoxylic acid of the general formula (1) or a derivative or salt thereof. In the process, an 1-acyl derivative of adamantane having the formula (2): wherein R is a C1-C5 hydrocarbyl; CH2OH; CHO; COOH, is contacted with an oxidant under oxidizing conditions leading to the 3-hydroxyadamantaneglyoxylic acid (1) or the derivative or salt thereof.

PROCESS FOR THE PREPARATION OF ADAMANTANE DERIVATIVES

The invention relates to a process for the preparation of 3-hydroxyadamantaneglyoxylic acid of the general formula (1) or a derivative or salt thereof. In the process, an 1-acyl derivative of adamantane having the formula (2): wherein R is a C1-C5 hydrocarbyl; CH2OH; CHO; COOH, is contacted with an oxidant under oxidizing conditions leading to the 3-hydroxyadamantaneglyoxylic acid (1) or the derivative or salt thereof.