Home Cart 0 Sign in  

[ CAS No. 34582-32-6 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 34582-32-6
Chemical Structure| 34582-32-6
Structure of 34582-32-6 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 34582-32-6 ]

Related Doc. of [ 34582-32-6 ]

Alternatived Products of [ 34582-32-6 ]

Product Details of [ 34582-32-6 ]

CAS No. :34582-32-6 MDL No. :MFCD00038272
Formula : C13H23NO6 Boiling Point : -
Linear Structure Formula :- InChI Key :RAUQRYTYJIYLTF-QMMMGPOBSA-N
M.W : 289.32 Pubchem ID :7010517
Synonyms :
(S)-4-(tert-Butoxy)-3-((tert-butoxycarbonyl)amino)-4-oxobutanoic acid

Calculated chemistry of [ 34582-32-6 ]

Physicochemical Properties

Num. heavy atoms : 20
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.77
Num. rotatable bonds : 9
Num. H-bond acceptors : 6.0
Num. H-bond donors : 2.0
Molar Refractivity : 72.21
TPSA : 101.93 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) : -7.09 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.38
Log Po/w (XLOGP3) : 1.37
Log Po/w (WLOGP) : 1.7
Log Po/w (MLOGP) : 1.08
Log Po/w (SILICOS-IT) : 0.8
Consensus Log Po/w : 1.46

Druglikeness

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

Water Solubility

Log S (ESOL) : -1.9
Solubility : 3.62 mg/ml ; 0.0125 mol/l
Class : Very soluble
Log S (Ali) : -3.11
Solubility : 0.223 mg/ml ; 0.00077 mol/l
Class : Soluble
Log S (SILICOS-IT) : -1.55
Solubility : 8.12 mg/ml ; 0.0281 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 3.51

Safety of [ 34582-32-6 ]

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

Application In Synthesis of [ 34582-32-6 ]

* 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 [ 34582-32-6 ]
  • Downstream synthetic route of [ 34582-32-6 ]

[ 34582-32-6 ] Synthesis Path-Upstream   1~9

  • 1
  • [ 34582-32-6 ]
  • [ 81323-58-2 ]
YieldReaction ConditionsOperation in experiment
95%
Stage #1: With 4-methyl-morpholine; isobutyl chloroformate In 1,2-dimethoxyethane at -15℃; for 0.166667 h;
Stage #2: With sodium tetrahydroborate; water In 1,2-dimethoxyethane at -15℃; for 0.0833333 h;
1 b) tert-Butyl N-(tert-butoxycarbonyl)-L-homoserinate
To a solution of Boc-L-Asp-OtBu (3.00 g, 10.4 mmol) in 1,2-dimethoxyethane (10 mL) was added at -15 °C 4-methylmorpholine (1.14 mL, 10.4 mmol) and isobutyl chloroformate (1.35 mL, 10.4 mmol).
After stirring for 10 min at -15 °C the precipitate was filtered off and washed with cold 1,2-dimethoxyethane (20 mL).
To the filtrate was added at -15 °C a solution of sodium borohydride (0.59 g, 15.6 mmol) in water (5 mL).
After 5 min water (250 mL) was added.
The reaction mixture was extracted with ethyl acetate (3 x 100 mL), the combined organic layers dried over sodium sulphate, and concentrated under reduced pressure to give the title compound.
Yield: 2.70 g, 9.81 mmol, 95 percent.
MS (ESIpos): m/z = 276 [M+H]+
1H-NMR (400MHz, CHLOROFORM-d): δ [ppm]= 1.46 (s, 9H), 1.48 (s, 9H), 1.51 - 1.58 (m, 1H), 2.09 - 2.20 (m, 1H), 3.45 (br. s., 1H), 3.55 - 3.76 (m, 2H), 4.31 - 4.40 (m, 1H), 5.35 (d, 1H).
95%
Stage #1: With 4-methyl-morpholine; isobutyl chloroformate In 1,2-dimethoxyethane at -15℃; for 0.166667 h;
Stage #2: With sodium tetrahydroborate In 1,2-dimethoxyethane; water at -15℃; for 0.0833333 h;
To a solution of Boc-L-Asp-OtBu (3.00 g, 10.4 mmol) in 1 ,2-dimethoxyethane (10 mL) was added at -15 ° C 4-methylmorpholine (1.14 mL, 10.4 mmol) and isobutyl chloroformate (1 .35 mL, 10.4 mmol). After stirring for 10 min at -15 °C the precipitate was filtered off and washed with cold 1 ,2-dimethoxyethane (20 mL). To the filtrate was added at -1 5 ° C a solution of sodium borohydride (0.59 g, 15.6 mmol) in water (5 mL). After 5 min water (250 mL) was added. The reaction mixture was extracted with ethyl acetate (3 x 100 mL), the combined organic layers dried over sodium sulphate, and concentrated under reduced pressure to give the title compound. Yield: 2.70 g, 9.81 mmol, 95 percent.MS (ESIpos): m/z = 276 [M+H]+ 1H-NMR (400MHz, CHLOROFORM-d): δ [ppm]= 1 .46 (s, 9H), 1 .48 (s, 9H), 1.51 - 1 .58 (m, 1 H), 2.09 - 2.20 (m, 1 H), 3.45 (br. s., 1 H), 3.55 - 3.76 (m, 2H), 4.31 - 4.40 (m, 1 H), 5.35 (d, 1 H).
90% With sodium tetrahydroborate; (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 0℃; for 3 h; Cooling with ice N,N-Diisopropylethylamine (DIEA, 1.38mL, 7.9mmol) was added to a stirred suspension of 1-tert-butyl N-(tert-butoxycarbonyl)-l-aspartate (1.759g, 6.1mmol) and benzotriazole-1- yloxytris-(dimethylamino)phosphonium hexafluorophosphate (BOP, 3.496g, 7.9mmol) in dry THF (30mL) stirred at ambient temperature. Stirring was continued at the same temperature for 10min before the flask was placed in an ice-water bath. NaBH4 (301mg, 7.9mmol) was then added in small portions. After completion of the addition, stirring was continued at 0°C for another 3h. The solvent was removed by rotary evaporation. The residue was taken up in EtOAc (25mL) and washed in turn with 1N HCl (8mL×3), saturated NaHCO3 (8mL×3) and brine (8mL) before being dried over anhydrous Na2SO4. Removal of the solvent by rotary evaporation and column chromatography (1:1 PE/EtOAc) on silica gel gave (S)-9b28 as a colorless oil (1.510g, 5.5mmol, 90percent): [α]D22+9.3 (c 1.0, CHCl3); 1H NMR (500MHz, CDCl3) δ 5.39 (d, J=6.3Hz, 1H), 4.31–4.22 (m, 1H), 3.72–3.53 (m, 2H), 3.40–3.00 (br s, 1H), 2.11–2.00 (m, 1H), 1.58–1.48 (m, 1H), 1.41 (s, 9H), 1.39 (s, 9H); 13C NMR (125MHz, CDCl3) δ 171.9, 156.4, 82.1, 80.1, 58.1, 50.9, 36.1, 28.1, 27.8.
87%
Stage #1: With chloroformic acid ethyl ester; triethylamine In tetrahydrofuran at -10 - -5℃; for 0.5 h;
Stage #2: With sodium tetrahydroborate In tetrahydrofuran; water at 20℃; for 4 h; Cooling with ice
Stage #3: With hydrogenchloride In tetrahydrofuran; waterCooling with ice
Acid 6 (0.733 g, 2.54 mmol) was dissolved in 5 mL THF in a 50 mL round bottom flask and the solution was cooled to -10 0C. To this solution Et3N (0.39 mL, 2.79 mmol) and ethyl chloroformate (0.27 mL, 2.79 mmol) were added dropwise. After stirring -10 to -5 0C for 30 min, the reaction mixture was filtered off. To a mixture OfNaBH4 (0.203 g, 5.33 mmol) with 2 mL H2O in a 100 mL two-neck flask cooled with an ice bath was added above filtrate slowly. The mixture was stirred at room temperature for further 4 h and was then acidified with 1 M HCl until the PH = 2 - 3 under the cooling with ice bath. The organic phase was collected and water phase was extracted with EtOAc (20 ML x 3). The organic phases were combined, washed with Sat. NaHCO3 (20 mL) and brine (20 mL), and dried with MgSO4. The filtrate was evaporated in vacuo and the residue was purified by FC (EtOAc/Hexanes, 35/65 to 45/55, vol/vol) to provide 7 (0.618 g, 87percent): [α]25D = -39.9 (c = 1.0, EtOH) [lit [α]25D = -37.5 (c = 1.0, EtOH)]; 1H NMR (200 MHz, CDCl3) .pound.5.35 (br s, 1 H), 4.36 (br s, 1 H), 3.77-3.57 (m, 2 H), 2.92 (br s, 1 H), 2.20-2.05 (m, 2 H), 1,48 (s, 9 H), 1.45 (s, 9 H); 13C NMR (50 MHz, CDCl3) .pound.172.1, 156.6, 82.3, 80.3,58.5, 51.3, 36.44, 28.4, 28.1; HRMS calcd for C13H25NaNO5 (M + Na)+: 298.1630, found:298.1632.Ref: K. Ramsamy, Richard K. Olsen, Thomas Emary. Synthesis, 1982, 42-43
79%
Stage #1: With 4-methyl-morpholine In tetrahydrofuran at 0℃; for 0.5 h;
Stage #2: With isobutyl chloroformate In tetrahydrofuran at 0 - 20℃;
Stage #3: With sodium tetrahydroborate In tetrahydrofuran; methanol for 16 h;
Intermediate D-I - tert-butyl N-(tert-butoxycarbonyl)-L-homoserinate was prepared as follows:To a solution of N-Boc-aspartic acid tert-butyl ester (5 g, 17.3 mmol) in anhydrous THF (20 mL) was added ΝMM (2.85 mL, 26 mmol) at 0 0C. After 30 minutes at 0 0C, isobutyl chloro formate (3.14 mL, 24 mmol) was added and the reaction stirred at RT for 3 hours. The reaction was then treated with NaBH4 (1.31 g, 34.6 mmol) and anhydrous MeOH (2 mL) and stirred for a further 16 hours. The reaction mixture was then dissolved in EtOAc (100 mL) and washed with water (100 mL) and brine (100 mL), then dried (MgSO4) and concentrated under reduced pressure. The crude was purified by column chromatography (EtOAc / heptane 1 :1) to afford the desired product (3.76 g, 79 percent). m/z = 276 [M+H]+.
72%
Stage #1: With 1-hydroxy-pyrrolidine-2,5-dione; dicyclohexyl-carbodiimide In ethyl acetate at 20℃;
Stage #2: With sodium tetrahydroborate In 1,4-dioxane; water at 0 - 20℃; for 2 h;
In 100 ml round bottom flask is added tert-butoxy carbonyl 2.89g N - aspartic acid tert-butyl - (Boc - Asp - OtBu, compound 1) and 1.29g N - hydroxysuccinimide, adding 50 ml ethyl acetate to dissolve, then is added under mixing 2.26g dicyclohexyl carbodiimide, continuing to stir at room temperature overnight. Filtering to remove the insoluble matter and rotates on the Rotavapor screwed out of the ethyl acetate, the residue dissolved under stirring 50 ml 1, 4 - dioxane and add 0.76g sodium borohydride, the mixture on ice bath cooling to 0 °C slowly dripping after 3 ml water, then removed ice continue to react at room temperature for 2 hours. Add 10 ml saturated ammonium chloride solution stirring 10 minutes, in the Rotavapor after removing the dioxane, aqueous phase for the remaining 100 ml ethyl acetate is divided into 4 extracting; after extracting state in 20 ml water and 20 ml saturated salt water all washing twice, anhydrous magnesium sulfate drying, in the Rotavapor turns on lathe does on, then for 1:3 ethyl acetate/cyclohexane as developing agent carrying out column chromatography separation, to obtain 2.00g N - tert butoxycarbonyl - homoserine tert-butyl (Boc - HoSer - OtBu, compound 2), yield by about 72percent.

Reference: [1] Patent: EP2322500, 2011, A1, . Location in patent: Page/Page column 26-27
[2] Patent: WO2011/57986, 2011, A1, . Location in patent: Page/Page column 53
[3] Organic and Biomolecular Chemistry, 2017, vol. 15, # 31, p. 6656 - 6667
[4] Organic Letters, 2001, vol. 3, # 20, p. 3153 - 3155
[5] Tetrahedron, 2017, vol. 73, # 9, p. 1265 - 1274
[6] Patent: WO2011/20018, 2011, A1, . Location in patent: Page/Page column 23-24
[7] Journal of the American Chemical Society, 2011, vol. 133, # 4, p. 1122 - 1133
[8] MedChemComm, 2013, vol. 4, # 5, p. 833 - 838
[9] Tetrahedron, 2001, vol. 57, # 30, p. 6557 - 6566
[10] Patent: WO2010/43867, 2010, A1, . Location in patent: Page/Page column 48-49
[11] Patent: CN106046047, 2016, A, . Location in patent: Paragraph 0048; 0049; 0050
[12] Tetrahedron Letters, 1990, vol. 31, # 26, p. 3759 - 3762
[13] Synthesis, 1982, # 1, p. 42 - 43
[14] Heterocycles, 1997, vol. 44, # 1, p. 519 - 530
[15] Journal of Medicinal Chemistry, 1999, vol. 42, # 14, p. 2633 - 2640
[16] Australian Journal of Chemistry, 1992, vol. 45, # 8, p. 1225 - 1240
[17] Journal of Peptide Science, 2012, vol. 18, # 10, p. 620 - 625
[18] Amino Acids, 2013, vol. 44, # 2, p. 443 - 448
[19] Russian Journal of General Chemistry, 2013, vol. 83, # 4, p. 777 - 778[20] Zh. Obshch. Khim., 2013, vol. 83, # 4, p. 697 - 698
[21] Molecular Pharmaceutics, 2014, vol. 11, # 11, p. 3852 - 3866
[22] ChemBioChem, 2016, vol. 17, # 18, p. 1738 - 1751
[23] Tetrahedron Letters, 2017, vol. 58, # 12, p. 1194 - 1197
[24] Tetrahedron Letters, 2017, vol. 58, # 26, p. 2551 - 2553
  • 2
  • [ 80963-08-2 ]
  • [ 34582-32-6 ]
YieldReaction ConditionsOperation in experiment
100% With hydrogen In ethanol for 3 h; A mixture of the ester 5 (1.04 g, 2.74 mmol) and 10percent Pd/C (0.2 g) in absolute EtOH (20 rnL) was shaken with hydrogen at 50 psi for 3 h. This mixture was then filtered and the filtrate was concentrated under vacuum to give a white crystalline solid 6 (0.79 g, 100percent): mp 97 - 99 0C (lit.1 97 - 98 0C; lit.2 98 - 100 0C); [α]24D = - 16.9 (c = 1.0, EtOH) and [α]23 5D = -23.6 (c = 1.5, MeOH) [lit2 [α]22D = + 19.6 (c = 1.0, CHCl3); lit3 [α]25D = -7.4 (c = 2.0, MeOH)]; 1H NMR (200 MHz, CDCl3) .pound.10.33 (br s, 1 H), 5.48 (d, 1 H, J= 8.0 Hz), 4.45 (t, 1 H, J= 4.0 Hz), 3.02 (dd, 1 H, J1 = 17.0 Hz, J2 = 4.0 Hz), 2.81 (dd, 1 H, J1 = 111 Hz, J2 = 4.6 Hz), 1.45 (br s, 18 H); 13C NMR (50 MHz, CDCl3) .pound.175.8, 169.9, 155.7, 82.4, 80.2, 50.5, 36.8, 28.3, 27.9; HRMS calcd for C13H23NaNO6 (M + Na)+: 312.1423, found: 312.1420.Ref: 1. C. C. Yang, R. B. Merrifeld. The Journal of Organic Chemistry 1976, 41, 1032-1041 2. Robert M. Adlington, Jack E. Baldwin, David Catterick, Gareth J. Pareth J. Pritchard. J. Chem. Soc, Perkin Trans. 1, 1999, 855-866
Reference: [1] Journal of the Chemical Society - Perkin Transactions 1, 1999, # 8, p. 855 - 866
[2] Tetrahedron, 2001, vol. 57, # 30, p. 6557 - 6566
[3] Patent: WO2011/20018, 2011, A1, . Location in patent: Page/Page column 23
[4] Journal of the American Chemical Society, 2011, vol. 133, # 4, p. 1122 - 1133
[5] Journal of Organic Chemistry, 1993, vol. 58, # 9, p. 2369 - 2376
[6] Molecular Pharmaceutics, 2014, vol. 11, # 11, p. 3852 - 3866
  • 3
  • [ 34582-31-5 ]
  • [ 34582-32-6 ]
YieldReaction ConditionsOperation in experiment
94% With water; sodium hydroxide In methanol at 20℃; for 3 h; To a solution of tBu ester 10 (1.65 g, 5.44 mmol) in MeOH (3.45 mL) was added 2M NaOH (2.47 mL). After stirring at room temperature for 3 h, MeOH was removed at reduced pressure and the remaining aqueous layer washed with ether. The aqueous layer was then acidified to pH 2 with 1M HCl and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, and concentrated in vacuo. Purification on silica gel column chromatography (hexane/EtOAc = 3/1) afforded 11 as a colorless solid (1.48 g, 5.11 mmol, 94percent)
1.52 g With water; lithium hydroxide In tetrahydrofuran at 0 - 20℃; for 20.5 h; 0.2 N solution of LiOH (38 mL, 7.6 mmol) was added to a solution of 6.9 mmol of N-Boc-diester 10 or 11 in 38 mL of THF cooled to 0 °C. The mixture was stirred at 0 °C for 30 min, then for 20 h at room temperature. The solution was evaporated by half, 20 mL of 5 percent aqueous solution of NaHCO3 was added, the mixture was washed with Et2O (2 × 15 mL). Aqueous layer was acidified with citric acid to pH 3–4, the reaction products were extracted with Et2O (4 × 20 mL). The organic layer was washed with brine (50 mL), dried over Na2SO4, evaporated. The residue was recrystallized from a hexane–EtOAc, 85 : 15 mixture. (S)-4-tert-Butoxy-3-(tert-butoxycarbonylamino)-4-oxobutanoic acid (4). Yield 1.52 g (76 percent). Colorless powder, mp 109.0 °C (hexane–EtOAc) (97–98 °C [21], 98–100 °C [24], 97–99 °C [28], 99–100 °C [23], 104.8 °C [25], 105–106 °C [41], 106 °C [20]), [α]D20 –23.9 (c 1.0, MeOH) [α]D23.5 –23.6 (c 1.5, MeOH) [28]. 1H NMR spectrum (400 MHz, CDCl3, 25 °C), δ, ppm (conformers A and B, 8 : 2): 1.45 s (9H, t-Bu), 1.46 s (9H, t-Bu), 2.83 d.d (1H, H3B, J 17.1, 4.1 Hz), 3.01 d.d (1H, H3A, J 17.1, 4.2 Hz), 4.30 br.s [0.2H, H2 (B)], 4.43–4.48 m [0.8H, H2 (A)], 5.45 d [0.8H, NH (A), J 7.5 Hz], 5.93 br.s [0.2H, NH (B)]. 13C NMR spectrum (125 MHz, CDCl3, 25 °C), d, ppm (conformers A and B): 27.83 (3C, A and B), 28.29 (3C, A and B), 36.85 (A and B), 50.36 (A), 51.73 (B), 80.11 (A), 81.33 (B), 82.56 (A and B), 155.51 (A), 155.84 (B), 169.58 (B), 169.78 (A), 174.74 (B), 176.25 (A). Found, percent: C 53.76; H8.14; N 4.78. C13H23NO6. Calculated, percent: C 53.97; H 8.01; N 4.84.
Reference: [1] Tetrahedron Letters, 2017, vol. 58, # 12, p. 1194 - 1197
[2] Journal of Organic Chemistry, 1988, vol. 53, # 9, p. 1900 - 1903
[3] Tetrahedron Letters, 2003, vol. 44, # 28, p. 5251 - 5253
[4] Russian Journal of Organic Chemistry, 2017, vol. 53, # 5, p. 769 - 776[5] Zh. Org. Khim., 2017, vol. 53, # 5, p. 756 - 762,7
  • 4
  • [ 7536-58-5 ]
  • [ 34582-32-6 ]
Reference: [1] Tetrahedron, 2001, vol. 57, # 30, p. 6557 - 6566
[2] Journal of Organic Chemistry, 1993, vol. 58, # 9, p. 2369 - 2376
[3] Patent: WO2011/20018, 2011, A1,
[4] Journal of the American Chemical Society, 2011, vol. 133, # 4, p. 1122 - 1133
[5] Molecular Pharmaceutics, 2014, vol. 11, # 11, p. 3852 - 3866
  • 5
  • [ 24424-99-5 ]
  • [ 34582-32-6 ]
Reference: [1] Journal of Organic Chemistry, 1993, vol. 58, # 9, p. 2369 - 2376
[2] Journal of Organic Chemistry, 1988, vol. 53, # 9, p. 1900 - 1903
  • 6
  • [ 59768-74-0 ]
  • [ 34582-32-6 ]
Reference: [1] Tetrahedron Letters, 2003, vol. 44, # 28, p. 5251 - 5253
[2] Journal of Organic Chemistry, 1988, vol. 53, # 9, p. 1900 - 1903
[3] Tetrahedron Letters, 2017, vol. 58, # 12, p. 1194 - 1197
  • 7
  • [ 94347-11-2 ]
  • [ 34582-32-6 ]
Reference: [1] Journal of the Chemical Society - Perkin Transactions 1, 1999, # 8, p. 855 - 866
  • 8
  • [ 540-88-5 ]
  • [ 34582-32-6 ]
Reference: [1] Russian Journal of Organic Chemistry, 2017, vol. 53, # 5, p. 769 - 776[2] Zh. Org. Khim., 2017, vol. 53, # 5, p. 756 - 762,7
  • 9
  • [ 104072-49-3 ]
  • [ 34582-32-6 ]
Reference: [1] Russian Journal of Organic Chemistry, 2017, vol. 53, # 5, p. 769 - 776[2] Zh. Org. Khim., 2017, vol. 53, # 5, p. 756 - 762,7
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 34582-32-6 ]

Amino Acid

Chemical Structure| 13726-84-6

[ 13726-84-6 ]

Boc-Glu(OtBu)-OH

Similarity: 0.92

Chemical Structure| 71449-08-6

[ 71449-08-6 ]

Z-D-Asp(OtBu)-OH

Similarity: 0.81

Chemical Structure| 7764-95-6

[ 7764-95-6 ]

Boc-D-Ala-OH

Similarity: 0.79

Chemical Structure| 15761-38-3

[ 15761-38-3 ]

Boc-Ala-OH

Similarity: 0.79

Chemical Structure|

[ ]

Similarity: 0.74