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[ CAS No. 87691-27-8 ] {[proInfo.proName]}

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Chemical Structure| 87691-27-8
Chemical Structure| 87691-27-8
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Product Details of [ 87691-27-8 ]

CAS No. :87691-27-8 MDL No. :MFCD02094406
Formula : C10H17NO5 Boiling Point : -
Linear Structure Formula :- InChI Key :BENKAPCDIOILGV-BQBZGAKWSA-N
M.W : 231.25 Pubchem ID :688614
Synonyms :
N-Boc-cis-4-hydroxy-L-proline

Calculated chemistry of [ 87691-27-8 ]

Physicochemical Properties

Num. heavy atoms : 16
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.8
Num. rotatable bonds : 4
Num. H-bond acceptors : 5.0
Num. H-bond donors : 2.0
Molar Refractivity : 59.53
TPSA : 87.07 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) : -7.53 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.6
Log Po/w (XLOGP3) : 0.25
Log Po/w (WLOGP) : 0.06
Log Po/w (MLOGP) : -0.07
Log Po/w (SILICOS-IT) : -0.64
Consensus Log Po/w : 0.24

Druglikeness

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

Water Solubility

Log S (ESOL) : -1.17
Solubility : 15.7 mg/ml ; 0.068 mol/l
Class : Very soluble
Log S (Ali) : -1.64
Solubility : 5.31 mg/ml ; 0.023 mol/l
Class : Very soluble
Log S (SILICOS-IT) : 0.43
Solubility : 621.0 mg/ml ; 2.69 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 3.14

Safety of [ 87691-27-8 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 87691-27-8 ]

* 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 [ 87691-27-8 ]
  • Downstream synthetic route of [ 87691-27-8 ]

[ 87691-27-8 ] Synthesis Path-Upstream   1~19

  • 1
  • [ 87691-27-8 ]
  • [ 84348-37-8 ]
Reference: [1] Canadian Journal of Chemistry, 1982, vol. 60, # 23, p. 2903 - 2907
[2] Patent: CN106349237, 2017, A, . Location in patent: Paragraph 0043; 0044; 0051
  • 2
  • [ 84348-37-8 ]
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YieldReaction ConditionsOperation in experiment
99.1% With sodium tetrahydroborate In methanol at 0 - 5℃; The reducing agent (4.0 to 5.0 e.q.) was added to the solvent,Cold to a certain temperature,Add the substrate in batches to exotherm,HPLC monitoring reaction,Reaction is completed,The reaction solution was added to water,Cooling to 0 ~ 5C,With dilute hydrochloric acid pH 2 ~ 3, EA extraction(5X * 3). The combined organic phases were washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give the crude product. The crude productThe product was crystallized from a mixed solvent of ethyl acetate and alkane.
Reference: [1] Patent: CN106543062, 2017, A, . Location in patent: Paragraph 0021; 0024; 0027
[2] Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 7, p. 2253 - 2265
[3] Tetrahedron Letters, 1993, vol. 34, # 46, p. 7489 - 7492
[4] Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 1, p. 251 - 259
  • 3
  • [ 24424-99-5 ]
  • [ 618-27-9 ]
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YieldReaction ConditionsOperation in experiment
95% With sodium hydroxide In tetrahydrofuran; water Commercially available (Aldrich) compound 6 (525 mg, 4 mmol) was dissolved in water (10 mL) and THF (5 L). NaOH (aq) was added to give pH 9-10. Boc anhydride (959 mg, 4.4 mmol) was dissolved in THF (2 mL) and added to the reaction dropwise. The reaction was maintained at a pH 9-10 with NaOH (aq). Upon completion, the reaction was acidified to pH of 3 with dilute HC1 (aq) and extracted with EtOAc (2x). The organic extracts were dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a Boc-protected proline (compound 6a) as a solid. This solid was washed with hexanes (3x) and dried under high vacuum to give the intermediate (882 mg, 95percent) which was then dissolved in anhydrous DMF (5 mL).HOBt (641 mg, 4.18 mmol) and EDAC (874 mg, 4.56 mmol) were added and stirred for 15 minutes. Compound 2 (1.87 g, 4.2 mmol) and TEA (1.1 ml, 7.6 mmol) were added and the reaction was stirred for 4 hours. The reaction material was diluted with EtOAc and washed with saturated aqueous sodium bicarbonate solution (3x) and saturated aqueous sodium chloride solution. The organic extracts were dried over anhydrous sodium sulfate and concentrated under reduced pressure. The material was purified with CombiFlash (0-10percent MeOH in DCM) to give compound 7 (345mg, 15percent). Mass Spectrum (m/e): (M+H)+ 623.1, (M-H)- 620.6.
77% With sodium hydroxide In tetrahydrofuran; water at 20℃; To a solution of (2S,4S)-4-hydroxypyrrolidine-2-carboxylic acid (3.9 g, 29.7 mmol) in THF (26.7 mL) and water(13.3 mL) was added di-tert-butyl dicarbonate (7.14 g, 32.7 mmol) and sodium hydroxide (2.0 N, 22.9 mL, 45.8 mmol)and the mixture stirred at room temperature overnight. The mixture then had 10percent citric acid (50 mL) added followed byEtOAc and extraction with water and brine. The organic extract was dried, filtered and concentrated to afford 5.31 g(77percent) of the title compound. MS (ESI) m/z 232 (M+H)+.
77% With sodium hydroxide; citric acid In tetrahydrofuran; water; ethyl acetate Example 127A
(2S,4S)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid
To a solution of (2S,4S)-4-hydroxypyrrolidine-2-carboxylic acid (3.9 g, 29.7 mmol) in THF (26.7 mL) and water (13.3 mL) was added di-tert-butyl dicarbonate (7.14 g, 32.7 mmol) and sodium hydroxide (2.0 N, 22.9 mL, 45.8 mmol) and the mixture stirred at room temperature overnight.
The mixture then had 10percent citric acid (50 mL) added followed by EtOAc and extraction with water and brine.
The organic extract was dried, filtered and concentrated to afford 5.31 g (77percent) of the title compound. MS (ESI) m/z 232 (M+H)+.
Reference: [1] Patent: WO2012/88156, 2012, A1, . Location in patent: Page/Page column 60-61
[2] Patent: EP2419404, 2015, B1, . Location in patent: Paragraph 0467
[3] Journal of Medicinal Chemistry, 1994, vol. 37, # 13, p. 2090 - 2099
[4] Journal of Organic Chemistry, 1996, vol. 61, # 10, p. 3534 - 3541
[5] Patent: WO2009/91856, 2009, A2, . Location in patent: Page/Page column 57
[6] Patent: US2010/267634, 2010, A1,
[7] Australian Journal of Chemistry, 2015, vol. 68, # 9, p. 1365 - 1372
[8] Patent: WO2015/192123, 2015, A1, . Location in patent: Page/Page column 78
[9] Patent: CN106349237, 2017, A, . Location in patent: Paragraph 0043; 0044; 0050
  • 4
  • [ 74844-91-0 ]
  • [ 87691-27-8 ]
YieldReaction ConditionsOperation in experiment
78%
Stage #1: With sodium hydroxide In ethanol; water for 4 h;
Stage #2: With citric acid In ethanol; water
Synthesis of Compound 74
N-Boc-cis-4-hydroxyproline methyl ester (73) (1.3 g, 5.3 mmol) was dissolved in ethanol (20 mL).
To the solution was added 2N NaOH aqueous solution (5.3 mL, 10.6 mmol).
The reaction was completed after 4 h, and was acidified with 10percent citric acid.
Ethanol was evaporated, and the final productproduct recovered by extraction with ethylacetate/water.
The organic layer was dried over sodium sulfate, filtered and concentrated to yield N-Boc-cis-4-hydroxyproline (74) (960 mg, 78percent)
78%
Stage #1: for 4 h;
Stage #2: With citric acid In water
N-Boc-cis-4-hydroxyproline methyl ester (73) (1.3 g, 5.3 mmol) was dissolved in ethanol (20 mL). To the solution was added 2 N NaOH aqueous solution (5.3 mL, 10.6 mmol). The reaction was completed after 4 h, and was acidified with 10percent citric acid. Ethanol was evaporated, and the final product recovered by extraction with ethylacetatetwater. The organic layer was dried over sodium sulfate, filtered, and concentrated to yield N-Boc-cis-4-hydroxyproline (74) (960 mg, 78percent)
51% With water; sodium hydroxide In methanol at 20℃; for 12 h; A mixture of 1 -tert-butyl 2-methyl (2S,4S)-4-hydroxypyrrolidine- 1 ,2-dicarboxylate (5 g, 20.39 mmol, 1.00 equiv), methanol (100 mL), water (20 mL), and sodium hydroxide (2.85 g, 71.26 mmol, 3.50 equiv) was stirred for 12 h at 20°C. The resulting solution was concentrated and dissolved in water. The pH value of the solution was adjusted to 3-4 with 5percent of HC1, extracted with ethyl acetate, dried over anhydrous sodium sulfate, and concentrated under vacuum. This resulted in the title compound (2.4 g, 51percent) as a white solid.
Reference: [1] Patent: US2006/199853, 2006, A1, . Location in patent: Page/Page column 47
[2] Patent: US2006/223884, 2006, A1, . Location in patent: Page/Page column 60
[3] Patent: WO2015/52264, 2015, A1, . Location in patent: Paragraph 01357; 01358
[4] Patent: US2008/39375, 2008, A1, . Location in patent: Page/Page column 58
[5] Patent: WO2008/19266, 2008, A2, . Location in patent: Page/Page column 43; 49
[6] Patent: US2008/267917, 2008, A1, . Location in patent: Page/Page column 36
[7] Patent: US2008/269228, 2008, A1, . Location in patent: Page/Page column 61
[8] Patent: US2009/123425, 2009, A1, . Location in patent: Page/Page column 39-40
[9] Patent: WO2010/33466, 2010, A1, . Location in patent: Page/Page column 60
[10] Patent: WO2006/119061, 2006, A2, . Location in patent: Page/Page column 38
  • 5
  • [ 87250-97-3 ]
  • [ 87691-27-8 ]
Reference: [1] Organic Letters, 2011, vol. 13, # 20, p. 5588 - 5591
  • 6
  • [ 13726-69-7 ]
  • [ 87691-27-8 ]
Reference: [1] Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 7, p. 2253 - 2265
[2] Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 1, p. 251 - 259
[3] Organic Letters, 2011, vol. 13, # 20, p. 5588 - 5591
  • 7
  • [ 440678-63-7 ]
  • [ 87691-27-8 ]
Reference: [1] Bulletin of the Chemical Society of Japan, 2002, vol. 75, # 11, p. 2517 - 2525
  • 8
  • [ 502442-53-7 ]
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Reference: [1] Bulletin of the Chemical Society of Japan, 2002, vol. 75, # 11, p. 2517 - 2525
  • 9
  • [ 502442-56-0 ]
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Reference: [1] Bulletin of the Chemical Society of Japan, 2002, vol. 75, # 11, p. 2517 - 2525
  • 10
  • [ 502442-62-8 ]
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Reference: [1] Bulletin of the Chemical Society of Japan, 2002, vol. 75, # 11, p. 2517 - 2525
  • 11
  • [ 502442-60-6 ]
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Reference: [1] Bulletin of the Chemical Society of Japan, 2002, vol. 75, # 11, p. 2517 - 2525
  • 12
  • [ 502442-58-2 ]
  • [ 87691-27-8 ]
Reference: [1] Bulletin of the Chemical Society of Japan, 2002, vol. 75, # 11, p. 2517 - 2525
  • 13
  • [ 24424-99-5 ]
  • [ 87691-27-8 ]
Reference: [1] Organic Letters, 2011, vol. 13, # 20, p. 5588 - 5591
[2] Patent: CN106543062, 2017, A,
  • 14
  • [ 51-35-4 ]
  • [ 87691-27-8 ]
Reference: [1] Organic Letters, 2011, vol. 13, # 20, p. 5588 - 5591
[2] Patent: CN106543062, 2017, A,
  • 15
  • [ 87250-97-3 ]
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Reference: [1] Journal of Fluorine Chemistry, 2008, vol. 129, # 9, p. 781 - 784
[2] RSC Advances, 2014, vol. 4, # 5, p. 2482 - 2490
  • 16
  • [ 502442-64-0 ]
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Reference: [1] Bulletin of the Chemical Society of Japan, 2002, vol. 75, # 11, p. 2517 - 2525
  • 17
  • [ 1332341-02-2 ]
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Reference: [1] RSC Advances, 2014, vol. 4, # 5, p. 2482 - 2490
  • 18
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  • [ 203866-14-2 ]
Reference: [1] Journal of the American Chemical Society, 2005, vol. 127, # 45, p. 15923 - 15932
  • 19
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  • [ 401564-36-1 ]
Reference: [1] Patent: CN106349237, 2017, A,
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