61477-40-5

Basic information

• Product Name: (R)-3-AMINO-1-BUTANOL
• Synonyms: R-3-amino-1-butanol;(3R)-3-Amino-1-butanol;1-Butanol,3-aMino-, (3R)-;(-)-(R)-3-aMinopropan-1-ol;(3R)-3-aMinobutan-1-ol;R-3-aMnio-butanol;Dolutegravir INT 2;(R)-3-AMINO-1-BUTANO
• CAS NO: 61477-40-5
• Molecular Formula: C₄H₁₁NO
• Molecular Weight: 89.14
• EINECS: 1592732-453-0
• Product Categories: Dolutegravir intermediate
• Mol File: 61477-40-5.mol
• Article Data: 40

Chemical Properties

• Boiling Point: 168℃
• Flash Point: 56℃
• Appearance: /
• Density: 0.927
• Refractive Index: 1.4530 to 1.4570
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• PKA: 15.00±0.10(Predicted)
• CAS DataBase Reference: (R)-3-AMINO-1-BUTANOL(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-3-AMINO-1-BUTANOL(61477-40-5)
• EPA Substance Registry System: (R)-3-AMINO-1-BUTANOL(61477-40-5)

Safety Data

• RIDADR: 2735
• HazardClass: 8
• PackingGroup: Ⅲ
• Hazardous Substances Data: 61477-40-5(Hazardous Substances Data)

Usage

Description

(R)-3-AMINO-1-BUTANOL is an alcohol organic compound, which is a key intermediate for many chiral drugs.

Chemical Properties

Colorless Liquid

Synthesis

Release of (R)-3-amino-1-butanol From the (S)-mandelic Salt Thereof; The (S)-mandelic salt of (R)-3-amino-1-butanol obtained in Example 1.1 (372 g, 1.54 mol) was suspended in triethanolamine (1 I) at 80° C., and the slurry was admixed with sodium methoxide (277.6 g, 1.54 mol; 30% in methanol), which gave a clear solution. This was heated to 100° C. and vacuum was applied. In a stepwise manner, a pressure of 750, 500, 250, 100, 50 and finally 20 mbar was applied. Through an attached Claisen distillation head (no return stream, no column), a clear distillate distilled over at a top temperature of 50 to 60° C., which was predominantly methanol. The pressure was then lowered further to 5 mbar, and (R)-3-amino-1-butanol distilled over at a top temperature of 76° C. The product was distilled once again in a water jet pump vacuum, in the course of which (R)-3-amino-1-butanol distilled over at 93° C. and 26 mbar. This gave 125 g (91% of theory) of (R)-3-amino-1-butanol as a colorless liquid with an optical purity of 99.6% ee.The optical purity of (R)-3-amino-1-butanol was determined by means of GC. To this end, (R)-3-amino-1-butanol (200 mg) and triethylamine (300 mg) were dissolved in diethyl ether (15 ml) and admixed with trifluoroacetic anhydride (0.6 ml). After stirring for 30 minutes, saturated ammonium chloride solution (5 ml) was added and the mixture was stirred for a further 15 minutes. Subsequently, the mixture was left to stand until two phases had formed, and a sample of the upper clear phase was analyzed by GC.Column: Hydrodex-TBDAc, 25 m×0.25 mm, Macherey & NagelInlet temperature: 250° C.Detector temperature: 250° C.Injection volume : 0.5 μlMode: SplitSplit ratio: 100:1Carrier gas: HeFlow: 0.8 ml/min (constant flow)Program:Initial temperature: 135° C.Initial time: 10 minRate: 5° C./minFinal temperature: 170° C.Final time: 35 minRetention times:R enantiomer: 17.68 min (N-trifluoroacylated) 21.23 min (N,O-bis-trifluoroacylated)S enantiomer: 18.24 min (N-trifluoroacylated) 20.11 min (N,O-bis-trifluoroacylated)

Synthetic route

(R)-3-acetamidobutanol → (R)-3-amino-1-butanol (61477-40-5)

Conditions	Yield
In ethanol at 70 - 80℃; Alkaline conditions;	97.5%

(-)-(3R)-3-((benzyloxycarbonyl)amino)butanol (866395-21-3) → (R)-3-amino-1-butanol (61477-40-5)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In ethanol at 50 - 60℃; under 3000.3 - 4500.45 Torr;	96%

(-)-tert-butyl [(R)-3-hydroxy-1-methylpropyl]carbamate (167216-17-3) → (R)-3-amino-1-butanol (61477-40-5)

Conditions	Yield
With trifluoroacetic acid In dichloromethane at 0 - 10℃;	95.8%
With hydrogenchloride In methanol; water at 25℃; for 6h; Green chemistry;	90%
With hydrogenchloride In methanol at 25℃;	0.5 g

(3R)-3-{[(1R)-1-phenylethyl]amino}butan-1-ol → (R)-3-amino-1-butanol (61477-40-5)

Conditions	Yield
With platinum on carbon In ethanol at 60℃; under 15001.5 Torr; for 10h; Reagent/catalyst;	95.4%

(R)-3-amino-1-butanol L-malate → (R)-3-amino-1-butanol (61477-40-5)

Conditions	Yield
With sodium methylate In methanol at 20℃; Solvent; Reagent/catalyst;	95.3%
With sodium hydroxide In isopropyl alcohol at 10 - 20℃; for 0.666667h;	12.9 g

(R)-3-amino-1-butanol tartarate → (R)-3-amino-1-butanol (61477-40-5)

Conditions	Yield
With potassium carbonate In acetonitrile at 40 - 45℃; Reagent/catalyst; Temperature;	95%

(R)-3-benzamido-1-butanol → (R)-3-amino-1-butanol (61477-40-5)

Conditions	Yield
In ethanol at 70 - 80℃; Alkaline conditions;	92.6%
With hydrogenchloride In water for 3h; Reflux;	90%

(R)-4-hydroxybutan-2-aminium (S)-2-hydroxy-2-phenylacetate (1236049-43-6) → (R)-3-amino-1-butanol (61477-40-5)

Conditions	Yield
With triethanolamine; sodium methylate In methanol at 80 - 100℃; under 3.75038 - 562.556 Torr;	91%
With sodium methylate In methanol at 20℃; for 2h;	35 g
With sodium methylate In methanol at 65℃; for 17h;

(R)-3-aminobutanol tartrate → (R)-3-amino-1-butanol (61477-40-5)

Conditions	Yield
With potassium carbonate In methanol at 45 - 50℃; for 12h;	90%

(R)-3-aminobutanoic acid (3775-73-3) → (R)-3-amino-1-butanol (61477-40-5)

Conditions	Yield
With sodium tetrahydroborate; trifluoroacetic acid In tetrahydrofuran at 20℃; Reagent/catalyst; Temperature; Solvent; Inert atmosphere; Cooling with ice;	84.3%
With sodium tetrahydroborate; zinc(II) chloride In tetrahydrofuran at 20 - 60℃; for 3.5h; Autoclave;	54%

(R)-3-benzamido-1-butanol → (R)-3-amino-1-butanol (61477-40-5) + benzoic acid (65-85-0)

Conditions	Yield
With hydrogenchloride for 5h; Heating;	A 83% B 37.2 g

1-(tert-butyldimethylsilyloxy)-3-aminobutane (245728-81-8) → (R)-3-amino-1-butanol (61477-40-5)

Conditions	Yield
With tetrabutyl ammonium fluoride In tetrahydrofuran for 1h;	80%

(R)-3-amino-butyric acid ethyl ester hydrochloride → (R)-3-amino-1-butanol (61477-40-5)

Conditions	Yield
Stage #1: (R)-3-amino-butyric acid ethyl ester hydrochloride With sodium hydrogencarbonate In water at 20℃; for 0.25h; Cooling with ice; Stage #2: With potassium borohydride In ethanol at 20℃; for 12h;	77%

(R)-3-aminobutanoic acid methyl ester hydrochloride (139243-54-2) → (R)-3-amino-1-butanol (61477-40-5)

Conditions	Yield
Stage #1: (R)-3-aminobutanoic acid methyl ester hydrochloride With sodium hydrogencarbonate In water for 0.25h; Cooling with ice; Stage #2: With potassium borohydride In methanol at 20℃; for 12h;	76%

(R)-methyl 3-aminobutanoate hydrochloride (6078-06-4, 83509-89-1, 102522-53-2, 103189-63-5) → (R)-3-amino-1-butanol (61477-40-5)

Conditions	Yield
With RuH(η1-BH4)(dppp)((R,R)-dpen); hydrogen In tetrahydrofuran at 80℃; under 37503.8 Torr; for 16h; Autoclave;	62%
With hydrogen; C40H39BN2P2Ru In tetrahydrofuran at 80℃; under 26252.6 - 37503.8 Torr; for 14h; Product distribution / selectivity;	n/a

(3R)-3-methyl-3-[((1S)-1-phenylethyl)amino]propan-1-ol (60920-20-9) → (R)-3-amino-1-butanol (61477-40-5)

Conditions	Yield
With hydrogen; palladium on activated charcoal In ethanol

3-aminobutanoic acid ethyl ester (5303-65-1) → (+)-(S)-3-aminopropan-1-ol (61477-39-2) + (R)-3-amino-1-butanol (61477-40-5)

Conditions	Yield
With lithium aluminium tetrahydride Yield given. Yields of byproduct given. Title compound not separated from byproducts;

methyl 3-((methoxycarbonyl)amino)-3-methylpropanoate (116173-78-5, 116173-72-9) → (R)-3-amino-1-butanol (61477-40-5)

Conditions	Yield
With lithium aluminium tetrahydride; hydrogen bromide 1.) AcOH; 2.) THF; Multistep reaction;

2-hydroxymethyl-N-(3-hydroxy-1-methyl-propyl)-benzamide (866395-51-9) → 2-benzofuran-1(3H)-one (87-41-2) + (R)-3-amino-1-butanol (61477-40-5)

Conditions	Yield
With acetic acid at 80℃;

(3R)-3-{benzyl[(1R)-1-phenylethyl]amino}butanol (899806-42-9) → (R)-3-amino-1-butanol (61477-40-5)

Conditions	Yield
With hydrogen; palladium hydroxide on carbon In methanol under 1551.49 Torr; for 24h;

tert-butyl (R)-3-amino-3-methyl-propionate (120686-16-0) → (R)-3-amino-1-butanol (61477-40-5)

Conditions	Yield
With potassium hydroxide; aluminium trichloride In diethyl ether; water

C8H13NO3 → (R)-3-amino-1-butanol (61477-40-5)

Conditions	Yield
With potassium hydroxide In ethanol; water at 20 - 85℃; for 2h;

1-Hydroxy-3-butanone (590-90-9) → (R)-3-amino-1-butanol (61477-40-5)

Conditions	Yield
With SEC-BUTYLAMINE; magnesium chloride In aq. phosphate buffer; dimethyl sulfoxide at 15℃; for 24h; Reagent/catalyst; Solvent; Temperature; Enzymatic reaction;	0.45 g
With glucose dehydrogenase; ammonium hydroxide; D-glucose; NAD; ammonium chloride; lysozyme; DNase I In water at 30℃; for 24h; Reagent/catalyst; Enzymatic reaction; enantioselective reaction;	n/a

(R)-3-amino-1-butanol (61477-40-5) + methyl 1-(2,2-dihydroxyethyl)-4-oxo-3-[(phenylmethyl)oxy]-1,4-dihydro-2-pyridinecarboxylate (1206102-08-0) → (4R,12aS)-7-(benzyloxy)-4-methyl-3,4,12,12a-tetrahydro-2H-pyrido[1′,2’:4,5] pyrazino[2,1-b][1,3]oxazine-6,8-dione (1206102-09-1)

Conditions	Yield
With acetic acid In toluene at 90℃; for 3.5h;	96%
With acetic acid In toluene at 90℃; for 2.5h; Product distribution / selectivity;	83%
With acetic acid In methanol; toluene at 90℃; for 2.5h; Reagent/catalyst; Temperature;	83%
With acetic acid In toluene at 90℃; for 2h; diastereoselective reaction;	80%

di-tert-butyl dicarbonate (24424-99-5) + (R)-3-amino-1-butanol (61477-40-5) → (-)-tert-butyl [(R)-3-hydroxy-1-methylpropyl]carbamate (167216-17-3)

Conditions	Yield
With triethylamine In dichloromethane at 25℃; for 16h;	91.3%
With triethylamine In dichloromethane at 20 - 24℃; for 4h;	80%
With triethylamine In dichloromethane at 20℃; for 4h;
With triethylamine In dichloromethane at 0 - 20℃; for 1h;

(R)-3-amino-1-butanol (61477-40-5) + benzaldehyde (100-52-7) → (R)-3-(benzylamino)butan-1-ol

Conditions	Yield
Stage #1: (R)-3-amino-1-butanol; benzaldehyde In methanol at 20℃; for 1h; Stage #2: With methanol; sodium tetrahydroborate at 0 - 20℃; for 2.33333h;	90%

(R)-3-amino-1-butanol (61477-40-5) + methyl 5-(2,4-difluorobenzylcarbamoyl)-3-methoxy-4-oxo-1-(2-oxoethyl)-1,4-dihydropyridine-2-carboxylate → (4R,12aS)-N-(2,4-difluorobenzyl)-7-methyloxy-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido [1',2',:4,5]pyrazino[2,1-b] [1,3]oxazine-9-carboxamide (1335210-35-9) + N-(2,4-difluorobenzyl)-7-methoxy-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxamide + (R)-N-(2,4-difluorobenzyl)-2-(4-hydroxybutan-2-yl)-9-methoxy-1,8-dioxo-1,8-dihydro-2H-pyrido[1,2-a]pyrazine-7-carboxamide

Conditions	Yield
In toluene; acetonitrile at 100℃; under 5171.62 Torr; Flow reactor;	A n/a B n/a C 88%

(R)-3-amino-1-butanol (61477-40-5) + C18H17NO7 (1246617-67-3) → C21H22N2O6 (1357289-10-1)

Conditions	Yield
With acetic acid In methanol; toluene at 90℃; for 3h;	81%

methyl 3-(benzyloxy)-5-(2,4-difluorobenzylcarbamoyl)-4-oxo-1-(2-oxoethyl)-1,4-dihydropyridine-2-carboxylate (1229006-25-0) + (R)-3-amino-1-butanol (61477-40-5) → (4R,12aS)-7-(benzyloxy)-N-(2,4-difluorobenzyl)-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1′,2’:4,5]-pyrazino[2,1-b][1,3]oxazine-9-carboxamide (1206102-11-5)

Conditions	Yield
With acetic acid In dichloromethane at 140℃; Microwave irradiation;	81%
With acetic acid In methanol; toluene at 90℃; for 2h;	65%
With acetic acid In methanol; toluene at 120℃; for 4h;	0.2 g

(R)-3-amino-1-butanol (61477-40-5) + C22H26F2N2O7 → C22H23F2N3O5

Conditions	Yield
Stage #1: C22H26F2N2O7 With methanesulfonic acid; acetic acid In acetonitrile at 25 - 70℃; for 9h; Stage #2: (R)-3-amino-1-butanol In acetonitrile at 65 - 70℃; for 5h;	81%

4-tolyl iodide (624-31-7) + (R)-3-amino-1-butanol (61477-40-5) → (R)-N-(4-hydroxybutan-2-yl)-p-toluidine

Conditions	Yield
With copper(l) iodide; potassium carbonate; L-proline In dimethyl sulfoxide at 120℃; for 12h; Inert atmosphere;	79%

(R)-3-amino-1-butanol (61477-40-5) + C20H21NO7 (1246616-87-4) → (4R,12aS)-3,4,6,8,12,12a-hexahydro-4-methyl-6,8-dioxo-7-(phenylmethoxy)-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxylic acid ethyl ester (1357289-04-3)

Conditions	Yield
With acetic acid In methanol; toluene for 3h; Reflux;	78%

(R)-3-amino-1-butanol (61477-40-5) + C20H17N5O3S → C24H26N6O3S

Conditions	Yield
Stage #1: (R)-3-amino-1-butanol; C20H17N5O3S In tetrahydrofuran for 0.166667h; Inert atmosphere; Stage #2: With N-ethyl-N,N-diisopropylamine; HATU In tetrahydrofuran for 2h; Reflux;	76%

(R)-3-amino-1-butanol (61477-40-5) + C19H20F2N2O7 → C23H29F2N3O7

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 2h;	76%

(R)-3-amino-1-butanol (61477-40-5) + tetraethyl 7-oxabicyclo[2.2.1]hepta-2,5-diene-2,3,5,6-tetracarboxylate → C26H42N2O10

Conditions	Yield
In neat (no solvent) at 20℃; Schlenk technique;	74%

(R)-3-amino-1-butanol (61477-40-5) → C4H9N3O

Conditions	Yield
Stage #1: (R)-3-amino-1-butanol With copper(II) sulfate; triethylamine In water; acetonitrile at 0℃; for 0.0833333h; Inert atmosphere; Stage #2: With imidazole-1-sulfonyl azide hydrochloride In water; acetonitrile at 0 - 20℃; for 2.16667h; Inert atmosphere;	74%

(R)-3-amino-1-butanol (61477-40-5) + C20H20F2N2O6 → C22H23F2N3O5

Conditions	Yield
With acetic acid In toluene at 80 - 90℃; for 24h;	71%
With acetic acid In methanol; toluene at 25 - 90℃; for 24h;	61%

Upstream product

• 5303-65-1 3-aminobutanoic acid ethyl ester 
• 866395-21-3 (-)-(3R)-3-((benzyloxycarbonyl)amino)butanol 
• 590-90-9 1-Hydroxy-3-butanone 
• 3775-73-3 (R)-3-aminobutanoic acid 
• 139243-54-2 (R)-3-aminobutanoic acid methyl ester hydrochloride 
• 146293-15-4 (R)-3-amino-butyric acid ethyl ester hydrochloride 
• 167216-17-3 (-)-tert-butyl [(R)-3-hydroxy-1-methylpropyl]carbamate 
• 1236049-43-6 (R)-4-hydroxybutan-2-aminium (S)-2-hydroxy-2-phenylacetate 
• 6078-06-4 (R)-methyl 3-aminobutanoate hydrochloride 
• 120686-16-0 tert-butyl (R)-3-amino-3-methyl-propionate 
• 899806-42-9 (3R)-3-{benzyl[(1R)-1-phenylethyl]amino}butanol 
• 866395-51-9 2-hydroxymethyl-N-(3-hydroxy-1-methyl-propyl)-benzamide 
• 245728-81-8 1-(tert-butyldimethylsilyloxy)-3-aminobutane 
• 116173-78-5 methyl 3-((methoxycarbonyl)amino)-3-methylpropanoate 

Downstream Products

• 1206102-09-1 (4R,12aS)-7-(benzyloxy)-4-methyl-3,4,12,12a-tetrahydro-2H-pyrido[1′,2’:4,5] pyrazino[2,1-b][1,3]oxazine-6,8-dione 
• 1537863-65-2 (R)-3-(phenylmethylsulfonamido)butyl phenylmethanesulfonate 
• 1335210-35-9 (4R,12aS)-N-(2,4-difluorobenzyl)-7-methyloxy-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido [1',2',:4,5]pyrazino[2,1-b] [1,3]oxazine-9-carboxamide 
• 1357289-24-7 C₂₈H₂₉F₂N₃O₆ 
• 1206102-11-5 (4R,12aS)-7-(benzyloxy)-N-(2,4-difluorobenzyl)-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1′,2’:4,5]-pyrazino[2,1-b][1,3]oxazine-9-carboxamide 
• 1357289-10-1 C₂₁H₂₂N₂O₆ 
• 1357289-04-3 (4R,12aS)-3,4,6,8,12,12a-hexahydro-4-methyl-6,8-dioxo-7-(phenylmethoxy)-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxylic acid ethyl ester 
• 1236049-43-6 (R)-4-hydroxybutan-2-aminium (S)-2-hydroxy-2-phenylacetate 
• 1335210-34-8 (4R,12aS)-7-methoxy-4-methyl-6,8-dioxo-3,4,6,8, 12,12a-hexahydro-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxylic acid 
• 245728-73-8 (R)-2-(4-hydroxybutan-2-yl)isoindoline-1,3-dione 

Relevant articles and documents

Refining process of R-3-amino n-butyl alcohol

The invention discloses a refining process of R-3-amino n-butyl alcohol, and belongs to the technical field of organic chemical engineering. According to the refining process of R-3-amino n-butyl alcohol, firstly, 4-hydroxy- 2-butanone and hydroxylamine hydrochloride are adopted for an oximation reaction, then an oximation product is hydrogenated, then L-malic acid is added to form resolution salt, then absolute ethyl alcohol is utilized for refining, and after dissociation, R-3-amino n-butyl alcohol with high optical purity can be obtained. The refining process disclosed by the invention is low in cost, environment-friendly and more beneficial to industrial production.

Biochemical and Structural Characterization of an (R)-Selective Transaminase in the Asymmetric Synthesis of Chiral Hydroxy Amines

An (R)-selective transaminase RbTA with excellent stereoselectivity (>99% ee) in the asymmetric amination of hydroxy ketones was identified. Biochemical characterization showed that RbTA exhibited the highest activity toward 4-hydroxy-2-butanone among reported enzymes, and that it has broad substrate specificity, including for aliphatic, aromatic, and alicyclic ketones. Crystallization of RbTA were performed, as were molecular docking and mutagenesis studies. Residue Tyr125 plays a key role in substrate recognition by forming a hydrogen bond with hydroxy ketone. The applicability of the enzyme was determined in preparative-scale synthesis of (R)-3-amino-1-butanol, demonstrating the potential of RbTA as a green biocatalyst for production of value-added chiral hydroxy amines. This study provides an efficient tool for enzymatic synthesis of chiral hydroxy amines, as well as structural insight into substrate recognition by transaminases in the asymmetric amination of hydroxy ketones. (Figure presented.).

Synthetic method of (R)-3- n-aminobutanol (by machine translation)

The invention belongs to, the field (R)- 3 - of pharmaceutical and chemical engineering, and particularly relates to a method for. preparing a product (R)- 3 - with good chemical purity, and optical, purity by, a, preparation method of a chiral drug midbody . (by machine translation)