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Chemical Structure| 159991-23-8
Chemical Structure| 159991-23-8
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Product Details of [ 159991-23-8 ]

CAS No. :159991-23-8 MDL No. :MFCD00270343
Formula : C9H17NO4 Boiling Point : -
Linear Structure Formula :- InChI Key :PYNDHEONPQYIAN-ZCFIWIBFSA-N
M.W : 203.24 Pubchem ID :2761507
Synonyms :

Calculated chemistry of [ 159991-23-8 ]

Physicochemical Properties

Num. heavy atoms : 14
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.78
Num. rotatable bonds : 6
Num. H-bond acceptors : 4.0
Num. H-bond donors : 2.0
Molar Refractivity : 51.66
TPSA : 75.63 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.93 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.75
Log Po/w (XLOGP3) : 0.86
Log Po/w (WLOGP) : 1.37
Log Po/w (MLOGP) : 0.83
Log Po/w (SILICOS-IT) : 0.24
Consensus Log Po/w : 1.01

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.56

Water Solubility

Log S (ESOL) : -1.25
Solubility : 11.5 mg/ml ; 0.0568 mol/l
Class : Very soluble
Log S (Ali) : -2.03
Solubility : 1.89 mg/ml ; 0.00929 mol/l
Class : Soluble
Log S (SILICOS-IT) : -1.05
Solubility : 18.1 mg/ml ; 0.0889 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.6

Safety of [ 159991-23-8 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P273-P305+P351+P338 UN#:N/A
Hazard Statements:H315-H319-H335-H412 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 159991-23-8 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Upstream synthesis route of [ 159991-23-8 ]
  • Downstream synthetic route of [ 159991-23-8 ]

[ 159991-23-8 ] Synthesis Path-Upstream   1~14

  • 1
  • [ 3775-73-3 ]
  • [ 24424-99-5 ]
  • [ 159991-23-8 ]
YieldReaction ConditionsOperation in experiment
90% With triethylamine In 1,4-dioxane; water at 0 - 20℃; for 16 h; Intermediate 72: (4S,7R,10aS)-4-Amino-7-methylhexahydro-2H-pyrido[2, l- b] [ 1 ,3 ]thiazepin-5(7H)-one.A: (R)-3-(tert-Butoxycarbonylamino)butanoic acid [00344] To a stirred suspension of (R)-3-aminobutanoic acid (2.415 g, 23.42 mmol) in dioxane (15 mL) and water (15.00 mL) was added TEA (4.90 mL, 35.1 mmol) dropwise. To the resulting light brown solution cooled at 0 °C was added portionwise di-tert-butyl carbonate (4.69 g, 26.9 mmol). The mixture was then stirred at rt for 16 hr. The reaction mixture was partitioned between water (80 mL) and EtOAc (80 mL). The separated aqueous layer was washed with EtOAc and acidified with 1 M aqueous KHSO4 to pH = 3 and extracted with EtOAc (2x). The combined EtOAc extracts were washed with saturated aqueous NaCl (2x), dried over Na2S04, filtered and concentrated to give (R)-3- (tert-butoxycarbonylamino)butanoic acid (4.301 g, 21.16 mmol, 90percent yield) as a pale yellow solid. XH NMR (400 MHz, CDC13) δ ppm 4.92 (s, 1H), 4.14 - 3.96 (m, 2H), 2.56 (d, J = 5.2 Hz, 2H), 1.45 (s, 9H), 1.25 (d, J = 6.9 Hz, 3H).
Reference: [1] Patent: WO2012/125622, 2012, A1, . Location in patent: Page/Page column 135-136
[2] Chinese Chemical Letters, 2015, vol. 26, # 1, p. 103 - 107
[3] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 5, p. 1421 - 1425
[4] Angewandte Chemie - International Edition, 2018, vol. 57, # 31, p. 9707 - 9710[5] Angew. Chem., 2018, vol. 130, # 31, p. 9855 - 9858,4
  • 2
  • [ 24424-99-5 ]
  • [ 28267-25-6 ]
  • [ 159991-23-8 ]
YieldReaction ConditionsOperation in experiment
90% With sodium hydroxide In 1,4-dioxane; hexane; water H.
Preparation of N-Boc α-Methyl β-Alanine
A solution of a-methyl b-alanine hydrochloride (97.7 g, 0.70 mol) in water (1050 mL) and dioxane (1050 mL) the pH was adjusted to 8.9 with 2.9N NaOH solution.
This stirring solution was then treated with di-tert-butyl pyrocarbonate (183.3 g, 0.84 mol, 1.2 equivalents) all at once.
The pH of the solution was maintained between 8.7 and 9.0 by the periodic addition of 2.5N NaOH solution.
After 2.5 h the pH had stabilized and the reaction was judged to be complete.
The solution was concentrated on a rotary evaporator (the temperature was maintained at <40° C.).
The excess di-tert-butyl pyrocarbonate was removed by extraction with dichloromethane and then the aqueous solution was acidified with cold 1N HCl and immediately extracted with ethyl acetate (4*1000 mL).
The combined ethyl acetate extract was washed with brine, dried over anhyd.
MgSO4, filtered and concentrated on a rotary evaporator to give a thick oil 127.3 g, 90percent crude yield that was stirred with n-hexane whereupon crystals of pure product formed, 95.65 g, 67percent, mp 76-78° C., [α]d at; 25° C.=-11.8° C. (c=2.4, EtOH).
A second crop was obtained by concentration of the filtrate and dilution with hexane, 15.4 g, for a combined yield of 111.05 g, 78percent.
1H NMR (acetone D&6) 300 MHz 11.7 (brs, 1H), 6.05 (brs 1H), 3.35 (m, 1H), 3.22 (m, 1H), 2.50 (m, 1H), 1.45(s, 9H), 1.19 (d, J=7.3 Hz, 3H); 13C NMR (acetone D6) 177.01, 79.28, 44.44, 40.92, 29.08, 15.50.
Elemental analysis calc'd. for C9H17NO4: C, 53.19, H, 8.42; N, 6.89. Found: C, 53.36; H, 8.46; N, 6.99.
90% With sodium hydroxide In 1,4-dioxane; hexane; water H.
Preparation of N-Boc α-Methyl-β-Alanine
A solution of α-Methyl-β-Alanine hydrochloride (97.7 g, 0.70 mol) in water (1050 mL) and dioxane (1050 mL) the pH was adjusted to 8.9 with 2.9N NaOH solution.
This stirring solution was then treated with di-tert-butyl pyrocarbonate (183.3 g, 0.84 mol, 1.2 equivalents) all at once.
The pH of the solution was maintained between 8.7 and 9.0 by the periodic addition of 2.5N NaOH solution.
After 2.5 h the pH had stabilized and the reaction was judged to be complete.
The solution was concentrated on a rotary evaporator (the temperature was maintained at <40° C.).
The excess di-t-butyl pyrocarbonate was removed by extraction with dichloromethane and then the aqueous solution was acidified with cold 1N HCl and immediately extracted with ethyl acetate (4*1000 mL).
The combined ethyl acetate extract was washed with brine, dried over anhydrous MgSO4, filtered and concentrated on a rotary evaporator to give a thick oil 127.3 g, 90percent crude yield that was stirred with n-hexane whereupon crystals of pure product formed, 95.65 g, 67percent, mp 76-78° C., [a]D at; 25° C.=-11.8° C. (c=2.4, EtOH).
A second crop was obtained by concentration of the filtrate and dilution with hexane, 15.4 g, for a combined yield of 111.05 g, 78percent.
1H NMR (acetone D6) 300 MHz 11.7 (brs, 1H), 6.05 (brs 1H), 3.35 (m, 1H), 3.22 (m, 1H), 2.50 (m, 1H), 1.45(s, 9H), 1.19 (d, J=7.3 Hz, 3H); 13C NMR (acetone D&6) 177.01, 79.28, 44.44, 40.92, 29.08, 15.50.
Elemental analysis calc'd. for C5H,7NO4: C, 53.19, H, 8.42; N, 6.89. Found: C, 53.36; H, 8.46; N, 6.99.
90% With sodium hydroxide In 1,4-dioxane; hexane; water H.
Preparation of N-Boc α-Methyl β-Alanine STR96
A solution of a-methyl b-alanine hydrochloride (97.7 g, 0.70 mol) in water (1050 mL) and dioxane (1050 mL) the pH was adjusted to 8.9 with 2.9N NaOH solution.
This stirring solution was then treated with di-tert-butyl pyrocarbonate (183.3 g, 0.84 mol, 1.2 equivalents) all at once.
The pH of the solution was maintained between 8.7 and 9.0 by the periodic addition of 2.5N NaOH solution.
After 2.5 h the pH had stabilized and the reaction was judged to be complete.
The solution was concentrated on a rotary evaporator (the temperature was maintained at <40° C.).
The excess di-tert-butyl pyrocarbonate was removed by extraction with dichloromethane and then the aqueous solution was acidified with cold 1N HCl and immediately extracted with ethyl acetate (4*1000 mL).
The combined ethyl acetate extract was washed with brine, dried over anhyd.
MgSO4, filtered and concentrated on a rotary evaporator to give a thick oil 127.3 g, 90percent crude yield that was stirred with n-hexane whereupon crystals of pure product formed, 95.65 g, 67percent, mp 76-78° C., [α]d at;25° C.=-11.8° C. (c=2.4, EtOH).
A second crop was obtained by concentration of the filtrate and dilution with hexane, 15.4 g, for a combined yield of 111.05 g, 78percent.
1 H NMR (acetone D&6) 300 MHz 11.7 (brs, 1H), 6.05 (brs 1H), 3.35 (m, 1H), 3.22 (m, 1H), 2.50 (m, 1H), 1.45(s, 9H), 1.19 (d, J=7.3 Hz, 3H); 13 C NMR (acetone D6) 177.01, 79.28, 44.44, 40.92, 29.08, 15.50.
Elemental analysis calc'd. for C9 H17 NO4: C, 53.19, H, 8.42; N, 6.89. Found: C, 53.36; H, 8.46; N, 6.99.
90% With sodium hydroxide In 1,4-dioxane; hexane; water H.
Preparation of N-Boc α-Methyl β-Alanine STR93
A solution of a-methyl b-alanine hydrochloride (97.7 g, 0.70 mol) in water (1050 mL) and dioxane (1050 mL) the pH was adjusted to 8.9 with 2.9N NaOH solution.
This stirring solution was then treated with di-tert-butyl pyrocarbonate (183.3 g, 0.84 mol, 1.2 equivalents) all at once.
The pH of the solution was maintained between 8.7 and 9.0 by the periodic addition of 2.5N NaOH solution.
After 2.5 h the pH had stabilized and the reaction was judged to be complete.
The solution was concentrated on a rotary evaporator (the temperature was maintained at <40° C.).
The excess di-tert-butyl pyrocarbonate was removed by extraction with dichloromethane and then the aqueous solution was acidified with cold 1N HCl and immediately extracted with ethyl acetate (4*1000 mL).
The combined ethyl acetate extract was washed with brine, dried over anhyd.
MgSO4, filtered and concentrated on a rotary evaporator to give a thick oil 127.3 g, 90percent crude yield that was stirred with n-hexane whereupon crystals of pure product formed, 95.65 g, 67percent, mp 76-78° C., [α]d at; 25° C.=-11.8° C. (c=2.4, EtOH).
A second crop was obtained by concentration of the filtrate and dilution with hexane, 15.4 g, for a combined yield of 111.05 g, 78percent.
1 H NMR (acetone D&6) 300 MHz 11.7 (brs, 1H), 6.05 (brs 1H), 3.35 (m, 1H), 3.22 (m, 1H), 2.50 (m, 1H), 1.45(s, 9H), 1.19 (d, J=7.3 Hz, 3H); 13 C NMR (acetone D6) 177.01, 79.28, 44.44, 40.92, 29.08, 15.50.
Elemental analysis calc'd. for C9 H17 NO4: C, 53.19, H, 8.42; N, 6.89. Found: C, 53.36; H, 8.46; N, 6.99.
90% With sodium hydroxide In 1,4-dioxane; hexane; water H.
Preparation of N-Boc α-Methyl β-Alanine STR94
A solution of a-methyl b-alanine hydrochloride (97.7 g, 0.70 mol) in water (1050 mL) and dioxane (1050 mL) the pH was adjusted to 8.9 with 2.9N NaOH solution.
This stirring solution was then treated with di-tert-butyl pyrocarbonate (183.3 g, 0.84 mol, 1.2 equivalents) all at once.
The pH of the solution was maintained between 8.7 and 9.0 by the periodic addition of 2.5N NaOH solution.
After 2.5 h the pH had stabilized and the reaction was judged to be complete.
The solution was concentrated on a rotary evaporator (the temperature was maintained at <40° C.).
The excess di-tert-butyl pyrocarbonate was removed by extraction with dichloromethane and then the aqueous solution was acidified with cold 1N HCl and immediately extracted with ethyl acetate (4*1000 mL).
The combined ethyl acetate extract was washed with brine, dried over anhyd.
MgSO4, filtered and concentrated on a rotary evaporator to give a thick oil 127.3 g, 90percent crude yield that was stirred with n-hexane whereupon crystals of pure product formed, 95.65 g, 67percent, mp 76-78° C., [α]d at; 25° C.=-11.8° C. (c=2.4, EtOH).
A second crop was obtained by concentration of the filtrate and dilution with hexane, 15.4 g, for a combined yield of 111.05 g, 78percent.
1 H NMR (acetone D&6) 300 MHz 11.7 (brs, 1H), 6.05 (brs 1H), 3.35 (m, 1H), 3.22 (m, 1H), 2.50 (m, 1H), 1.45(s, 9H), 1.19 (d, J=7.3 Hz, 3H); 13 C NMR (acetone D6) 177.01, 79.28, 44.44, 40.92, 29.08, 15.50.
Elemental analysis calcd. for C9 H17 NO4: C, 53.19, H, 8.42; N, 6.89. Found: C, 53.36; H, 8.46; N, 6.99.
90% With sodium hydroxide In 1,4-dioxane; hexane; water H.
Preparation of N-Boc α-Methyl β-Alanine STR39
A solution of a-methyl b-alanine hydrochloride (97.7 g, 0.70 mol) in water (1050 mL) and dioxane (1050 mL) the pH was adjusted to 8.9 with 2.9N NaOH solution.
This stirring solution was then treated with di-tert-butyl pyrocarbonate (183.3 g, 0.84 mol, 1.2 equivalents) all at once.
The pH of the solution was maintained between 8.7 and 9.0 by the periodic addition of 2.5N NaOH solution.
After 2.5 h the pH had stabilized and the reaction was judged to be complete.
The solution was concentrated on a rotary evaporator (the temperature was maintained at <40° C.).
The excess di-tert-butyl pyrocarbonate was removed by extraction with dichloromethane and then the aqueous solution was acidified with cold 1N HCl and immediately extracted with ethyl acetate (4*1000 mL).
The combined ethyl acetate extract was washed with brine, dried over anhyd.
MgSO4, filtered and concentrated on a rotary evaporator to give a thick oil 127.3 g, 90percent crude yield that was stirred with n-hexane whereupon crystals of pure product formed, 95.65 g, 67percent, mp 76-78° C., [α]d at;25° C.=-11.8° C. (c=2.4, EtOH).
A second crop was obtained by concentration of the filtrate and dilution with hexane, 15.4 g, for a combined yield of 111.05 g, 78percent.
1 H NMR (acetone D&6) 300 MHz 11.7 (brs, 1H), 6.05 (brs 1H), 3.35 (m, 1H), 3.22 (m, 1H), 2.50 (m, 1H), 1.45(s, 9H), 1.19 (d, J=7.3 Hz, 3H); 13 C NMR (acetone D6) 177.01, 79.28, 44.44, 40.92, 29.08, 15.50.
Elemental analysis calc'd. for C9 H17 NO4: C, 53.19, H, 8.42; N, 6.89. Found: C, 53.36; H, 8.46; N, 6.99.
90% With sodium hydroxide In 1,4-dioxane; hexane; water H.
Preparation of N-Boc α-Methyl β-Alanine STR26
A solution of a-methyl b-alanine hydrochloride (97.7 g, 0.70 mol) in water (1050 mL) and dioxane (1050 mL) the pH was adjusted to 8.9 with 2.9N NaOH solution.
This stirring solution was then treated with di-tert-butyl pyrocarbonate (183.3 g, 0.84 mol, 1.2 equivalents) all at once.
The pH of the solution was maintained between 8.7 and 9.0 by the periodic addition of 2.5N NaOH solution.
After 2.5 h the pH had stabilized and the reaction was judged to be complete.
The solution was concentrated on a rotary evaporator (the temperature was maintained at <40° C.).
The excess di-tert-butyl pyrocarbonate was removed by extraction with dichloromethane and then the aqueous solution was acidified with cold 1N HCl and immediately extracted with ethyl acetate (4*1000 mL).
The combined ethyl acetate extract was washed with brine, dried over anhyd.
MgSO4, filtered and concentrated on a rotary evaporator to give a thick oil 127.3 g, 90percent crude yield that was stirred with n-hexane whereupon crystals of pure product formed, 95.65 g, 67percent, mp 76°-78° C., [α]d at; 25° C.=-11.8° C. (c=2.4, EtOH).
A second crop was obtained by concentration of the filtrate and dilution with hexane, 15.4 g, for a combined yield of 111.05 g, 78percent.
1 H NMR (acetone D&6) 300 MHz 11.7 (brs, 1H), 6.05 (brs 1H), 3.35 (m, 1H), 3.22 (m, 1H), 2.50 (m, 1H), 1.45(s, 9H), 1.19 (d, J=7.3 Hz, 3H); 13 C NMR (acetone D6) 177.01, 79.28, 44.44, 40.92, 29.08, 15.50.
Elemental analysis calc'd. for C9 H17 NO4: C, 53.19, H, 8.42; N, 6.89. Found: C, 53.36; H, 8.46; N, 6.99.
90% With sodium hydroxide In 1,4-dioxane; hexane; water H.
Preparation of N-Boc α-Methyl β-Alanine STR86
A solution of a-methyl b-alanine hydrochloride (97.7 g, 0.70 mol) in water (1050 mL) and dioxane (1050 mL) the pH was adjusted to 8.9 with 2.9N NaOH solution.
This stirring solution was then treated with di-tert-butyl pyrocarbonate (183.3 g, 0.84 mol, 1.2 equivalents) all at once.
The pH of the solution was maintained between 8.7 and 9.0 by the periodic addition of 2.5N NaOH solution.
After 2.5 h the pH had stabilized and the reaction was judged to be complete.
The solution was concentrated on a rotary evaporator (the temperature was maintained at <40° C.).
The excess di-tert-butyl pyrocarbonate was removed by extraction with dichloromethaneand then the aqueous solution was acidified with cold 1N HCl and immediately extracted with ethyl acetate (4*1000 mL).
The combined ethyl acetate extract was washed with brine, dried over anhyd.
MgSO4,filtered and concentrated on a rotary evaporator to give a thick oil 127.3 g, 90percent crude yield that was stirred with n-hexane whereupon crystals of pure product formed, 95.65 g, 67percent, mp 76°-78° C., [α]d at; 25° C.=-11.8° C. (c=2.4, EtOH).
A second crop was obtained by concentration of the filtrate and dilution with hexane, 15.4 g, for a combined yield of 111.05 g, 78percent.
1 H NMR (acetone D&6) 300 MHz 11.7 (brs, 1H), 6.05 (brs 1H), 3.35 (m, 1H), 3.22 (m, 1H), 2.50 (m, 1H), 1.45 (s, 9H), 1.19 (d, J=7.3 Hz, 3H); 13 C NMR (acetone D6) 177.01, 79.28, 44.44, 40.92, 29.08, 15.50.
Elemental analysis calc'd. for C9 H17 NO4: C, 53.19, H, 8.42; N, 6.89. Found: C, 53.36; H, 8.46; N, 6.99.
90% With sodium hydroxide In 1,4-dioxane; hexane; water H.
Preparation of N-Boc α-Methyl β-Alanine STR86
A solution of a-methyl b-alanine hydrochloride (97.7 g, 0.70 mol) in water (1050 mL) and dioxane (1050 mL) the pH was adjusted to 8.9 with 2.9N NaOH solution.
This stirring solution was then treated with di-tert-butyl pyrocarbonate (183.3 g, 0.84 mol, 1.2 equivalents) all at once.
The pH of the solution was maintained between 8.7 and 9.0 by the periodic addition of 2.5N NaOH solution.
After 2.5 h the pH had stabilized and the reaction was judged to be complete.
The solution was concentrated on a rotary evaporator (the temperature was maintained at <40° C.).
The excess di-tert-butyl pyrocarbonate was removed by extraction with dichloromethane and then the aqueous solution was acidified with cold 1N HCl and immediately extracted with ethyl acetate (4*1000 mL).
The combined ethyl acetate extract was washed with brine, dried over anhyd.
MgSO4, filtered and concentrated on a rotary evaporator to give a thick oil 127.3 g, 90percent crude yield that was stirred with n-hexane whereupon crystals of pure product formed, 95.65 g, 67percent, mp 76°-78° C., [α]d at; 25° C.=-11.8° C. (C=2.4, EtOH).
A second crop was obtained by concentration of the filtrate and dilution with hexane, 15.4 g, for a combined yield of 111.05 g, 78percent.
1 H NMR (acetone D&6) 300 MHz 11.7 (brs, 1H), 6.05 (brs 1H), 3.35 (m, 1H), 3.22 (m, 1H), 2.50 (m, 1H), 1.45(s, 9H), 1.19 (d, J=7.3 Hz, 3H); 13 C NMR (acetone D6) 177.01, 79.28, 44.44, 40.92, 29.08, 15.50.
Elemental analysis calc'd. for C9 H17 NO4: C, 53.19, H, 8.42; N, 6.89. Found: C, 53.36; H, 8.46; N, 6.99.

Reference: [1] Patent: US6335460, 2002, B1,
[2] Patent: US6538006, 2003, B1,
[3] Patent: US5968942, 1999, A,
[4] Patent: US6046190, 2000, A,
[5] Patent: US6060476, 2000, A,
[6] Patent: US6156768, 2000, A,
[7] Patent: US5578606, 1996, A,
[8] Patent: US5744481, 1998, A,
[9] Patent: US5843946, 1998, A,
  • 3
  • [ 3775-73-3 ]
  • [ 34619-03-9 ]
  • [ 159991-23-8 ]
YieldReaction ConditionsOperation in experiment
93.5% With sodium carbonate In water at 25℃; Green chemistry Sequentially put 103g of R-3-aminobutyric acid,105g sodium carbonate,218g di-tert-butyl carbonate,Add to the reaction flask containing 500 mL of water,React at 25 °C for 2-6 hours,After the reaction is completed, adjust the pH to 3-4 with 2N hydrochloric acid.The product was extracted twice with 500 mL of ethyl acetate.Spin dry,That is, N-Boc-(R)-3-aminobutyric acid (I),The white solid was 190 g, the yield was 93.5percent, and the content was 98percent (HPLC method).
Reference: [1] Patent: CN108424370, 2018, A, . Location in patent: Paragraph 0087; 0088
  • 4
  • [ 24424-99-5 ]
  • [ 159991-23-8 ]
YieldReaction ConditionsOperation in experiment
90% With sodium hydroxide In 1,4-dioxane; hexane; water H.
Preparation of N-Boc α-Methyl β-Alanine STR161
A solution of α-methyl β-alanine hydrochloride (97.7 g, 0.70 mol)in water (1050 mL) and dioxane (1050 mL) the pH was adjusted to 8.9 with 2.9N NaOH solution.
This stirring solution was then treated with di-tert-butyl pyrocarbonate (183.3 g, 0.84 mol, 1.2 equivalents) all at once.
The pH of the solution was maintained between 8.7 and 9.0 by the periodic addition of 2.5N NaOH solution.
After 2.5 h the pH had stabilized and the reaction was judged to be complete.
The solution was concentrated on a rotary evaporator (the temperature was maintained at <40° C.).
The excess di-tert -butyl pyrocarbonate was removed by extraction with dichloromethane and then the aqueous solution was acidified with cold 1N HCl and immediately extracted with ethyl acetate (4*1000 mL).
The combined ethyl acetate extract was washed with brine, dried over anhyd.
MgSO4, filtered and concentrated on a rotary evaporator to give a thick oil 127.3 g, 90percent crude yield that was stirred with n-hexane whereupon crystals of pure product formed, 95.65 g, 67percent, mp 76°-78° C., [α]D at;25° C.=-11.8° C. (c=2.4, EtOH).
A second crop was obtained by concentration of the filtrate and dilution with hexane, 15.4 g, for a combined yield of 111.05 g, 78percent. 1H NMR (acetone D6) 300 MHz 11.7 (brs, 1H), 6.05 (brs 1H), 3.35 (m, 1H), 3.22 (m, 1H), 2.50 (m, 1H), 1.45(s, 9H), 1.19 (d, J=7.3 Hz, 3H); 13 C NMR (acetone D6) 177.01, 79.28, 44.44, 40.92, 29.08, 15.50.
Elemental analysis calc'd. for C9H17NO4: C, 53.19, H, 8.42; N, 6.89. Found: C, 53.36; H, 8.46; N, 6.99.
90% With sodium hydroxide In 1,4-dioxane; hexane; water H.
Preparation of N-Boc α-Methyl β-Alanine STR66
A solution of α-methyl β-alanine hydrochloride (97.7 g, 0.70 mol) in water (1050 mL) and dioxane (1050 mL) the pH was adjusted to 8.9 with 2.9N NaOH solution.
This stirring solution was then treated with di-tert-butyl pyrocarbonate (183.3 g, 0.84 mol, 1.2 equivalents) all at once.
The pH of the solution was maintained between 8.7 and 9.0 by the periodic addition of 2.5N NaOH solution.
After 2.5 h the pH had stabilized and the reaction was judged to be complete.
The solution was concentrated on a rotary evaporator (the temperature was maintained at <40° C.).
The excess di-tert-butyl pyrocarbonate was removed by extraction with dichloromethane and then the aqueous solution was acidified with cold 1N HCl and immediately extracted with ethyl acetate (4*1000 mL).
The combined ethyl acetate extract was washed with brine, dried over anhydrous MgSO4, filtered and concentrated on a rotary evaporator to give a thick oil 127.3 g, 90percent crude yield that was stirred with n-hexane whereupon crystals of pure product formed, 95.65 g, 67percent, mp 76°-78° C., [α]D, at; 25° C.=-11.8° C. (c=2.4, EtOH).
A second crop was obtained by concentration of the filtrate and dilution with hexane, 15.4 g, for a combined yield of 111.05 g, 78percent.
1 H NMR (acetone D&6) 300 MHz 11.7 (brs, 1H), 6.05 (brs 1H), 3.35 (m, 1H), 3.22 (m, 1H), 2.50 (m, 1H), 1.45(s, 9H), 1.19 (d, J=7.3 Hz, 3H); 13 C NMR (acetone D6) 177.01, 79.28, 44.44, 40.92, 29.08, 15.50.
Elemental analysis calc'd. for C9 H17 NO4: C, 53.19, H, 8.42; N, 6.89. Found: C, 53.36; H, 8.46; N, 6.99.
Reference: [1] Patent: US5475013, 1995, A,
[2] Patent: US5643924, 1997, A,
[3] Patent: EP396526, 1992, A3,
  • 5
  • [ 159877-47-1 ]
  • [ 159991-23-8 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 1996, vol. 6, # 19, p. 2253 - 2258
[2] Synlett, 2002, # 12, p. 2039 - 2040
[3] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 2, p. 576 - 585
  • 6
  • [ 24424-99-5 ]
  • [ 159991-23-8 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 5, p. 1274 - 1279
[2] Synlett, 2002, # 12, p. 2039 - 2040
[3] Angewandte Chemie - International Edition, 2000, vol. 39, # 20, p. 3635 - 3638
[4] Bioorganic and Medicinal Chemistry Letters, 1996, vol. 6, # 19, p. 2253 - 2258
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  • [ 43080-09-7 ]
  • [ 159991-23-8 ]
YieldReaction ConditionsOperation in experiment
37.1 g With ephedrine In ethanol at 70 - 75℃; 90 g of 3- (Boc-amino) butanoic acid was dissolved in 225 mL of ethanol, heated with stirring to 70-75 ° C., slowly at this temperature Dropping 58.5 g L-ephedrine 60 mL ethanol solution, dropping completed, incubated for 20 ~ 30 min, slowly cooled to 10 ~ 15 , suction filtered, dried to give carboxylate 78.5 g. Then 78.5 g of carboxylate was added to 200 mL of ethanol, heated to 70-75 ° C, Insulation 15 ~ 20 min, slowly reduced to 10 ~ 15 , suction filtration, dried to give carboxylate 75.3 g, this operation was repeated 2 times to give the carboxyl 69.2 g of acid salt and 99.7percent of ee value. Finally, 69.2 g of carboxylate is added to 195 mL of water, the pH is adjusted to 1-2 with concentrated hydrochloric acid, The mixture was extracted twice with 150 mL of ethyl acetate and the combined organic phases were concentrated until no fractions were obtained to give 37.1 g of the compound of formula I.
Reference: [1] Patent: CN106966912, 2017, A, . Location in patent: Paragraph 0015; 0016; 0017; 0018; 0019; 0020; 0021
  • 8
  • [ 186521-98-2 ]
  • [ 159991-23-8 ]
Reference: [1] Helvetica Chimica Acta, 1996, vol. 79, # 8, p. 2043 - 2066
[2] Journal of Peptide Science, 2012, vol. 18, # 9, p. 556 - 559
  • 9
  • [ 170367-68-7 ]
  • [ 159991-23-8 ]
Reference: [1] Organic Letters, 2015, vol. 17, # 3, p. 632 - 635
  • 10
  • [ 186581-53-3 ]
  • [ 3744-87-4 ]
  • [ 159991-23-8 ]
Reference: [1] Journal of Peptide Science, 2012, vol. 18, # 9, p. 556 - 559
  • 11
  • [ 869468-34-8 ]
  • [ 159991-23-8 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 5, p. 1274 - 1279
  • 12
  • [ 3744-87-4 ]
  • [ 159991-23-8 ]
Reference: [1] Journal of Peptide Science, 2012, vol. 18, # 9, p. 556 - 559
  • 13
  • [ 159991-23-8 ]
  • [ 497861-77-5 ]
Reference: [1] Patent: WO2012/125622, 2012, A1,
  • 14
  • [ 159991-23-8 ]
  • [ 167216-17-3 ]
YieldReaction ConditionsOperation in experiment
95% With sodium tetrahydroborate; boron trifluoride diethyl etherate In tetrahydrofuran at -20℃; Green chemistry 100 g of N-Boc-(R)-3-aminobutyric acid and 300 mL of tetrahydrofuran were placed in a reaction flask, 20.6 g of sodium borohydride was added in portions, the temperature was lowered to -20 °C, and 100 g of boron trifluoride etherate was slowly added dropwise. HPLC to determine whether the raw material reaction is complete. After completion of the reaction, the reaction was quenched by the addition of methanol, and the solvent was evaporated. Filter to remove solids,The filtrate was washed with 100 ml of saturated sodium bicarbonate.The organic phase was concentrated to give N-Boc-(R)-3-aminobutanol as a white solid, 88 g, yield 95percent, mp. 99.0percent (HPLC method).
91% With sodium tetrahydroborate; iodine In tetrahydrofuran at 0 - 30℃; 115 g of the compound of formula I was dissolved in 460 mL of tetrahydrofuran, cooled to 0~10 ° C. in an ice bath, 23.7 g of sodium borohydride was added in portions, the temperature was controlled at 0~10 ° C., and 165.4 g of elemental iodine Of 230 mL of tetrahydrofuran solution, the dropwise addition, and gradually warmed to 25 ~ 30 ° C,Liquid phase tracking is complete until the conversion of the raw material, 60 mL of water is added dropwise to quench the reaction, concentrated under reduced pressure to no distillate, 500 mL of methanol is added, the temperature is raised to 55-60 ° C., the solution is incubated for 0.5 h, mL water, drops After completion of the incubation, the mixture was stirred for 1 hour, then slowly cooled to 15-20 ° C, filtered and dried to obtain 97.4 g of the compound of formula II in a yield of 91percent.
Reference: [1] Patent: CN108424370, 2018, A, . Location in patent: Paragraph 0090; 0091
[2] Patent: CN106966912, 2017, A, . Location in patent: Paragraph 0022; 0023; 0024
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