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[ CAS No. 116457-91-1 ] {[proInfo.proName]}

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Chemical Structure| 116457-91-1
Chemical Structure| 116457-91-1
Structure of 116457-91-1 * Storage: {[proInfo.prStorage]}
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Product Details of [ 116457-91-1 ]

CAS No. :116457-91-1 MDL No. :MFCD29055252
Formula : C23H23NO3 Boiling Point : -
Linear Structure Formula :- InChI Key :LXAWQKKSNNYYEK-OAQYLSRUSA-N
M.W : 361.43 Pubchem ID :7438296
Synonyms :

Calculated chemistry of [ 116457-91-1 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 27
Num. arom. heavy atoms : 18
Fraction Csp3 : 0.17
Num. rotatable bonds : 8
Num. H-bond acceptors : 4.0
Num. H-bond donors : 2.0
Molar Refractivity : 104.74
TPSA : 58.56 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : Yes
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : Yes
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.85 cm/s

Lipophilicity

Log Po/w (iLOGP) : 3.18
Log Po/w (XLOGP3) : 3.74
Log Po/w (WLOGP) : 2.99
Log Po/w (MLOGP) : 3.29
Log Po/w (SILICOS-IT) : 4.03
Consensus Log Po/w : 3.45

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -4.4
Solubility : 0.0143 mg/ml ; 0.0000396 mol/l
Class : Moderately soluble
Log S (Ali) : -4.66
Solubility : 0.00787 mg/ml ; 0.0000218 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -7.44
Solubility : 0.0000132 mg/ml ; 0.0000000365 mol/l
Class : Poorly soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 3.0
Synthetic accessibility : 2.78

Safety of [ 116457-91-1 ]

Signal Word:Warning Class:
Precautionary Statements:P280-P302+P352 UN#:
Hazard Statements:H315-H319-H335 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 116457-91-1 ]

* 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.

  • Downstream synthetic route of [ 116457-91-1 ]

[ 116457-91-1 ] Synthesis Path-Downstream   1~24

  • 1
  • [ 76-83-5 ]
  • [ 5874-57-7 ]
  • [ 116457-91-1 ]
YieldReaction ConditionsOperation in experiment
99% With triethylamine; In chloroform; at 0℃; for 1h; D-serine methyl ester hydrochloride (40 g, 0.26 mol) was dissolved in chloroform (360 mL). Triethylamine (90 mL, 0.64 mol) was added at 0 C. Slowly added triphenylchloromethane (72 g, 0.26 mol), reaction for 1 hour. Add chloroform (200 mL) at room temperature. Wash with water (500 mL), The organic phase is dried over anhydrous sodium sulfate. Concentrated by suction filtration, Get the title compound(93 g, yield 99%).
97% With triethylamine; In 1,2-dichloro-ethane; at 50℃; for 12h; Put (D)-serine methyl ester hydrochloride (10.0g, 64mmol, 1.0equiv.,) into a three-necked flask, dissolve it in 150mL 1,2-dichloroethane, and add triethylamine (16.0g, 2.5equiv.,) , And then add TrtCl (15.4g, 1.0 equiv.) in batches. Then the reaction system was placed in an oil bath at 50 C. and heated and stirred for 12 hours. TLC detected that the reactants disappeared completely, and the reaction system was placed in an ice-water bath. When the internal temperature reached 10C, a saturated aqueous ammonium chloride solution was slowly added dropwise to quench the reaction. The chloroform layer was separated, washed with saturated brine, dried with anhydrous sodium sulfate, filtered to obtain the organic phase, evaporated to remove the solvent, and recrystallized in a petroleum ether/ethyl acetate mixed solvent to obtain 22.38 g of white solid (compound A). The yield was 97%.
95% With triethylamine; In dichloromethane; at 0 - 25℃; for 16h; Methyl Trityl-D-Serinate To a stirred solution of methyl-D-serinate hydrochloride (2 g, 12.8 mmol) in DCM (10 mL) at 0 C., triethylamine (6.1 mL, 45.9 mmol) was added. Trityl chloride (4.26 g, 15.3 mmol) was then added and the reaction mixture was stirred for 16 hours at room temperature. After completion of the reaction (monitored by TLC), the reaction mixture was quenched with water (20 mL) and the aqueous layer was extracted with DCM (2*30 mL). The combined organic layer was washed with water (30 mL) and brine (30 mL) and dried over anhydrous Na2SO4. The organic part was filtered and concentrated under vacuum. The resulting crude material was purified by Isolera column chromatography (eluent: 27% EtOAc/PE; silica gel: 230-400 mesh) to afford the title compound. Yield: 95% (2.5 g, white solid). 1H NMR (400 MHz, DMSO-d6): δ 7.43 (d, J=8.0 Hz, 6H), 7.29 (t, J=8.0 Hz, 6H), 7.20 (t, J=7.2 Hz, 3H), 4.95-4.92 (m, 1H), 3.63-3.51 (m, 1H), 3.46-3.40 (m, 1H), 3.24-3.18 (m, 1H), 3.13 (s, 3H), 2.82-2.71 (m, 1H).
92% With triethylamine; In dichloromethane; at -5 - 20℃; A compound of D- serine methyl ester hydrochloride (1000g, 6.45mol, 1eq) was dissolved in 5L of dichloromethane, was added triethylamine (1955g, 19.35mol, 3eq), maintaining the temperature at -5 ~ 5 , min after the batch was added triphenylmethyl chloride (2152g, 7.74mol, 1.2eq) was stirred at room temperature until the reaction is complete, water was added quenched liquid separation, the organic phase was washed with hydrochloric acid, TLC testing to confirm no triethylamine dried over anhydrous sodium sulfate, the solvent was concentrated to give a white solid, a -D- N- trityl-serine methyl ester. Yield 92%.
With triethylamine; In dichloromethane; at 0℃; for 12h;Inert atmosphere; General procedure: To a suspension of (S)-serine methyl ester hydrochloride (0.50 g, 3.2 mmol) in DCM (7 ml) at 0 C, under a nitrogen atmosphere, was added dropwise triethylamine (1.0 ml, 7.1 mmol), followed by a solution of triphenylmethyl chloride (0.91 g, 3.2 mmol) in DCM (2 ml). After stirring at 0 C for 12 h the white precipitate was filtered and the filtrate was concentrated in vacuo to yield a white solid which was dissolved in ethyl acetate (10 ml), washed with 1 M aqueou NaHCO3 solution (10 ml), 10% aqueous citric acid solution (10 ml) and water (10 ml). The organic layer was dried over anhydrous magnesium sulfate and concentrated in vacuo giving a white solid. Purification by flash column chromatography on silica gel in petroleum ether:ethyl acetate (4:1), gave N-trityl-(S)-serine methyl ester as a white solid (0.99 g, 86%).
With triethylamine; In dichloromethane; at 0℃; for 12h;Inert atmosphere; General procedure: N-Trityl-(S)-serine methylester. To a suspension of (S)-serine methyl ester hydrochloride (0.50 g, 3.2mmol) in DCM (7 ml) at 0 oC, under a nitrogen atmosphere, was added dropwise triethylamine (1.0 ml, 7.1 mmol), followed by a solution of triphenylmethyl chloride (0.91 g, 3.2 mmol) in DCM (2 ml). After stirring at 0 oC for 12 h the white precipitate was filtered and the filtrate was concentrated in vacuo to yield a white solid which was dissolved in ethyl acetate (10 ml), washed with 1 M aqueous NaHCO3 solution (10 ml), 10% aqueous citric acid solution (10 ml) and water (10 ml). The organic layer was dried over anhydrous magnesium sulfate and concentrated in vacuo giving a white solid. Purification by flash column chromatography on silica gel in petroleum ether:ethyl acetate(4:1), gave N-trityl-(S)-serine methyl ester as a white solid (0.99 g, 86%).
With triethylamine; In chloroform; at 0 - 20℃; for 1h; Example 1: Preparation of (R)-4-[(R)-3-amino-4-(2,4,5-trifluorophenvDbutanoyll- 3-(t-butoxymethyl)piperazin-2-one hydrochloride; Step 1: Preparation of (R)-methyl l-tritylaziridine-2-carboxylate; 200 g of D-serine methyl ester hydrochloride was added to 1.8 L of chloroform, and the reaction solution was cooled to 0C, to which 448 mL of triethylamine was then slowly added. 358.4 g of trityl chloride was slowly added to the reaction mixture which was then stirred for 1 hour. The reaction mixture was warmed to room temperature, and 1 L of chloroform was added thereto, followed by washing with 2.5 L of water. The organic layer was dried over magnesium sulfate and cooled to 0C, to which 484 mL of triethylamine and 15.7 g of 4- methylaminopyridine were then sequentially and slowly added. The reaction mixture was stirred for 5 min and 139 mL of methane sulfonyl chloride was slowly added thereto. The reaction mixture was warmed to room temperature, stirred for another 4 hours and then refluxed for 12 hours. The reaction mixture was cooled to room temperature, and washed with 4 L of water and then 3 L of brine. The organic layer was dried over magnesium sulfate and <n="17"/>concentrated to dryness under reduced pressure. 3 L of ethanol was added to the resulting residue which was then stirred. The resulting solids were filtered to afford 329 g of the title compound.IH NMR (400 MHz, CDC13): 7.42 to 7.49(m, 6H), 7.18 to 7.32(m, 9H), 7.68(s, IH),3.74(s, 3H), 2.24(m, IH), 1.87(m, IH), and 1.40(m, IH)
With triethylamine; In dichloromethane; at 0℃; for 24h;Inert atmosphere; (ft)-Methyl 3-Hydroxy-2-(λ/-tritylamino)propanoate (S. Bhatia and J. Hajdu, Tetrahedron Lett. 1998, 29, 31-34).; To a solution of D-serine methyl ester hydrochloride (20.00 g, 0.13 mol) and Et3N (35.82 mL, 0.26 mol) in CH2CI2 (80 mL) at 0 0C, was added in one portion a solution of TrCI (36.53 g, 0.13 mol) in CH2CI2 (80 mL). The mixture was allowed to stir at 0 0C (24 h) under Ar and then successively washed with 10% aqueous citric acid (120 mL) and saturated aqueous brine (120 mL). The organic layer was dried (Na2SO4) and evaporated in vacuo to yield 45.20 g (97%) of crude desired product as a pale yellow crystalline solid. The product was used for next step without further purification: Rf = 0.50 (1/1 EtOAc/hexanes); 1H NMR (CDCI3) δ 2.29 (br s, 1 H), 2.98 (br s, 1 H), 3.29 (S, OCH3), 3.51-3.60 (m, CHH'OH, CH), 3.64-3.74 (m, CHH'OH), 7.16-7.30 (m, 9 PhH), 7.47-7.50 (m, 6 PhH).

  • 2
  • [ 116457-91-1 ]
  • [ 124-63-0 ]
  • [ 116457-92-2 ]
YieldReaction ConditionsOperation in experiment
93% With triethylamine; In dichloromethane; at -10 - -5℃; for 1.5h; take -D- N- trityl-serine methyl ester (2000g, 5.54mol, 1eq) to 10L of methylene chloride, the insulation -10 ~ -5 ,Triethylamine (1000g, 9.9mol, 1.78eq) was added dropwise to the reaction system with stirring, was slowly added dropwise methanesulfonyl chloride (700g, 6.11mol,1.1 eq), 1.5 hours after the addition was complete, the reaction mixture was stirred, was added after the reaction was quenched with water, separated, the organic phase with brine pickledBrine, the organic phase was dried over anhydrous sodium sulfate, and rotary dried to give a brown solid, i.e. -N- methanesulfonyl-trityl-serine -D-Methyl ester in 93% yield.
With triethylamine; In tetrahydrofuran; at 0℃; for 0.5h; General procedure: Triethylamine (1.68 ml, 12.1 mmol) was added dropwise over 10 min to a stirred solution of N-trityl-(S)-serine methyl ester (2.0 g, 5.5 mmol) in THF (50 ml) at 0 C, followed by the dropwiseaddition of methanesulfonyl chloride (0.47 ml, 60.0 mmol) and the solution was stirred at 0 C for 30 mins giving the mesylate intermediate and was subsequently heated at reflux temperature for 48 h. After completion of the reaction, solvent was removed under reduced pressure. The resulting residue was dissolved in EtOAc (60 ml) and washed with 10% aqueous citric acid solution (3 x 20 ml), H2O (2 x 20 ml), saturated aqueous Na2CO3 solution (3 x 20 ml), H2O (2 x 20 ml) and brine (20 ml). The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. Purification by flash column chromatography on silica gel in petroleum ether:ethyl acetate (4:1), gave 1a as a cloudy oil (1.8 g, 95%).
With triethylamine; In dichloromethane; at 0℃;Inert atmosphere; (/?)-Methyl 1-Tritylaziridine-2-carboxylate (S. Kato et al., J. Chem. Soc, Perkin Trans. 1997, 1 , 3219-3225; J. Smrt et al., Experientia 1957, 15, 291).; Crude (R)-methyl 3- hydroxy-2-(λ/-tritylamino)propanoate (45.20 g, 0.13 mol) was dissolved in CH2CI2 (300 mL) and cooled to 0 0C under Ar. Methanesulfonyl chloride (10.64 mL, 0.14 mol) was added to the cooled solution, followed by the dropwise addition of Et3N (26.14 mL, 0.19 mol). The resulting solution was allowed to stir at 0 0C (30 min) and then successively washed with 10% aqueous citric acid (200 mL) and saturated aqueous brine (200 mL). After drying (Na2SO4) and evaporation of the solvent, the crude mesylate (53.30 g, 0.12 mol) was dissolved in DME (300 mL) and Et3N (33.73 mL, 0.24 mol) was added. The reaction mixture was stirred at 80 0C (48 h) and then evaporated in vacuo. The residue was dissolved in EtOAc (300 mL) and washed with 10% aqueous citric acid (200 mL) and saturated aqueous brine (200 mL). The organic layer was dried (Na2SO4) and evaporated in vacuo. The crude product was recrystallized (EtOH) to yield 30.81 g (74%) of desired product as a transparent crystal: mp 127-128 0C (Kato, S. et al., J. Chem. Soc, Perkin Trans. 1997, 1 , 3219-3225; mp 129-131 0C); [α]20D +94.7 (c 1.5, CHCI3) (Smrt, J. et al., <n="29"/>Experientia 1957, 15, 291 ; [Cx]20D +95 (c 1 , CHCI3)); Rf = 0.45 (1/5 EtOAc/hexanes); 1H NMR (CDCI3) δ 1.41 (dd, J = 1.7, 6.4 Hz, NCHH'CH), 1.89 (dd, J = 2.8, 6.4 Hz, CHH'CHN), 2.26 (dd, J = 1.7, 2.8 Hz, NCHH'CH), 3.76 (s, OCH3), 7.20-7.31 (m, 9 PhH), 7.48-7.52 (m, 6 PhH); 13C NMR (CDCI3) δ 28.8 (NCH2CH), 31.8 (CH2CHN), 52.2 (OCH3), 74.5 (NCPh3), 127.1 , 127.8, 129.4, 143.7 (3 C6H5), 172.0 (C(O)).
  • 3
  • [ 116457-91-1 ]
  • [ 160233-42-1 ]
YieldReaction ConditionsOperation in experiment
98% With methanesulfonyl chloride; triethylamine; In dichloromethane; at 0 - 20℃; for 24h; Dissolve 22.38g (62mmol, 1.0eq.) of the amino-protected product (Compound A) in dichloromethane, cool the system to 0C, and slowly add triethylamine (2.5eq., 11.0mL) and MsCl (1.5 equiv., 3.7mL). After the addition is complete, the ice-salt bath is removed, and the system is naturally restored to room temperature and stirred for 24 hours. TLC detects that the reactants have completely disappeared. The reaction is quenched by adding deionized water, and the dichloromethane layer is obtained by liquid separation. It was washed with saturated brine, dried with anhydrous sodium sulfate, evaporated to remove the solvent, and recrystallized in a mixed solvent of n-hexane/methyl tert-butyl ether to obtain 20.9 g of white solid (compound B) with a yield of 98%.
76% Methyl (2R)-3-hydroxy-2-(tritylamino)propanoate (93 g, 0.26 mol) soluble in chloroform (500mL), add triethylamine (95 mL, 0.68 mol) at 0 C And 4-dimethylaminopyridine (2.8 g, 26 mmol), after stirring for 5 minutes, methanesulfonyl chloride (28 mL, 0.36 mol) was added slowly. After reacting for 4 hours at room temperature, The mixture was heated to 62 C for 12 hours. The reaction solution was cooled to room temperature. Wash with water (800 mL) and saturated sodium chloride solution (600 mL), respectively. Dry over anhydrous sodium sulfate and concentrate by suction filtration. Ethanol (600 mL) was added to the residual solid.Stir for 10 minutes, filter, collect the filter cake, The title compound was obtained (67 g, yield 76%). It is a white solid.
With dmap; methanesulfonyl chloride; triethylamine; In chloroform; at 0 - 20℃; for 16h;Heating / reflux; Example 1: Preparation of (R)-4-[(R)-3-amino-4-(2,4,5-trifluorophenvDbutanoyll- 3-(t-butoxymethyl)piperazin-2-one hydrochloride; Step 1: Preparation of (R)-methyl l-tritylaziridine-2-carboxylate; 200 g of D-serine methyl ester hydrochloride was added to 1.8 L of chloroform, and the reaction solution was cooled to 0C, to which 448 mL of triethylamine was then slowly added. 358.4 g of trityl chloride was slowly added to the reaction mixture which was then stirred for 1 hour. The reaction mixture was warmed to room temperature, and 1 L of chloroform was added thereto, followed by washing with 2.5 L of water. The organic layer was dried over magnesium sulfate and cooled to 0C, to which 484 mL of triethylamine and 15.7 g of 4- methylaminopyridine were then sequentially and slowly added. The reaction mixture was stirred for 5 min and 139 mL of methane sulfonyl chloride was slowly added thereto. The reaction mixture was warmed to room temperature, stirred for another 4 hours and then refluxed for 12 hours. The reaction mixture was cooled to room temperature, and washed with 4 L of water and then 3 L of brine. The organic layer was dried over magnesium sulfate and <n="17"/>concentrated to dryness under reduced pressure. 3 L of ethanol was added to the resulting residue which was then stirred. The resulting solids were filtered to afford 329 g of the title compound.IH NMR (400 MHz, CDC13): 7.42 to 7.49(m, 6H), 7.18 to 7.32(m, 9H), 7.68(s, IH),3.74(s, 3H), 2.24(m, IH), 1.87(m, IH), and 1.40(m, IH)
  • 5
  • [ 116457-91-1 ]
  • [ 98-59-9 ]
  • (R)-3-(Toluene-4-sulfonyloxy)-2-(trityl-amino)-propionic acid methyl ester [ No CAS ]
  • 6
  • [ 116457-91-1 ]
  • (2S)-N-triphenylmethyl-3-iodoalanine methyl ester [ No CAS ]
  • 7
  • [ 116457-91-1 ]
  • (2S,6R)-N2-triphenylmethyl-N6-(9H-fluorenylmethoxycarbonyl)-lanthionine dimethyl ester [ No CAS ]
  • 8
  • [ 116457-91-1 ]
  • [ 167226-21-3 ]
  • 9
  • [ 116457-91-1 ]
  • [ 116457-94-4 ]
  • 10
  • [ 116457-91-1 ]
  • [ 116457-93-3 ]
  • 11
  • [ 116457-91-1 ]
  • [ 116457-95-5 ]
  • 12
  • [ 116457-91-1 ]
  • [ 116457-96-6 ]
  • 13
  • D-serine methyl ester [ No CAS ]
  • [ 76-83-5 ]
  • [ 116457-91-1 ]
YieldReaction ConditionsOperation in experiment
85% With triethylamine; In dichloromethane; for 2h; Step 2[00246] To a solution of D-Ser-OMe (LXXXVIII) in dry DCM was added TEA (1.2 eq). After the solution became clear, trityl chloride (1 eq in dry DCM) was added dropwise and stirred for 2 hours. The reaction mixture was washed with 2M HCI, brine and dried over anhydrous MgS04. The solvent was removed under reduced pressure to give the crude product as a colorless oil. The oil crystallized from Et20/hexane to produce pure (R)-methyl 3-hydroxy- 2-(tritylamino)propanoate (LXXXIX) as white solid (85% yield).
With triethylamine; In dichloromethane; at 0 - 20℃; 36.82 ml of triethylamine are added, at ambient temperature under nitrogen, to 20.00 g of the methyl ester derivative of (D)-serine in solution in 250 ml of dichloromethane. After cooling the reaction medium to 0 C., a solution of trityl chloride in 200 ml of dichloromethane is run in so as to maintain the temperature of the medium between 0 C. and 5 C. After a contact time of 3 hours at 5 C., the reaction medium is washed with a saturated NH4Cl solution, with water and with a saturated NaCl solution, dried over sodium sulfate and concentrated under vacuum. The residue is taken up in diethyl ether. The precipitate obtained is filtered off and 41.72 g of the expected product are isolated after drying in the form of a white solid.1H NMR (DMSO, 200 MHz): 2.80 ppm: d: 1H, 3.15-3.25 ppm: mt: 1H, 3.30 ppm: s: 3H, 3.35-3.50 ppm: mt: 1H, 3.55-3.70 ppm: mt: 1H, 4.90 ppm: t: 1H, 7.10-7.50 ppm: mt: 15H.
  • 14
  • [ 100-02-7 ]
  • [ 116457-91-1 ]
  • [ 944447-58-9 ]
YieldReaction ConditionsOperation in experiment
With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; at 20℃; for 0.333333h; 37.19 g of triphenylphosphine, 20.13 g of p-nitrophenol and 23.02 ml of diethyl azodicarboxylate are successively added, at ambient temperature under nitrogen, to 41.00 g of the product obtained above in solution in 1250 ml of tetrahydrofuran. After a contact time of 20 minutes, the reaction medium is diluted with ethyl acetate. The organic phase is washed with a saturated NaHCO3 solution and with a saturated NaCl solution, dried over sodium sulfate and concentrated under vacuum. The residue is chromatographed on silica (gradient: heptane 100 to heptane/ethyl acetate 70:30) to give 36.12 g of the expected product in the form of a white solid.1H NMR (CDCl3, 200 MHz): 2.90 ppm: d: 1H, 3.25 ppm: s: 3H, 3.70-3.80 ppm: mt: 1H, 4.05 ppm: dd: 1H, 4.30 ppm: dd: 1H, 6.90 ppm: d: 2H, 7.10-7.35 ppm: mt: 9H, 7.55 ppm: d: 6H, 8.15 ppm: d: 2H.
  • 15
  • [ 402-45-9 ]
  • [ 116457-91-1 ]
  • [ 1393477-17-2 ]
YieldReaction ConditionsOperation in experiment
50% Step 3[00247] To a solution of triphenylphosphine (3 eq) in dry THF under Argon was added diethylazodicarboxylate (3 eq) dropwise. The reaction mixture was stirred at room temperature for 15 minutes before adding a solution of 4-(trifluoromethyl)phenol (3eq in dry THF) dropwise. The reaction mixture was stirred at room temperature for 1 hour before adding (R)-methyl 3-hydroxy-2-(tritylamino)propanoate (LXXXIX) in dry THF in one portion. The reaction mixture was stirred at room temperature ovenight. The mixture was concentrated to dryness, treated with hexane and filtered. The residue was concentrated to dryness and purified by silica flash chromatography (EtOAc/hexane = 1 :5). Pure (R)-methyl 3-(4- (trifluoromethyl)phenoxy)-2-(tritylamino)propanoate (XC) was obtained as an off-white solid (50% yield).
  • 16
  • [ 116457-91-1 ]
  • [ 124-63-0 ]
  • C24H25NO5S [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: 1-Trityl-aziridine-2S-carboxylic acid methyl ester (1a). Triethylamine (1.68 ml, 12.1 mmol) was added dropwise over 10 min to a stirred solution of N-trityl-(S)-serine methyl ester (2.0g, 5.5 mmol) in THF (50 ml) at 0 oC, followed by the dropwise addition of methanesulfonyl chloride (0.47 ml, 60.0 mmol) and the solution was stirred at 0 oC for 30 mins giving the mesylate intermediate and was subsequently heated at reflux temperature for 48 h. After completion of the reaction, solvent was removed under reduced pressure. The resulting residue was dissolved in EtOAc (60 ml) and washed with 10% aqueous citric acid solution (3x 20 ml), H2O (2 x 20 ml), saturated aqueous Na2CO3 solution (3 x 20 ml), H2O (2 x 20 ml) and brine (20 ml). The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. Purification by flash column chromatography on silica gel in petroleum ether:ethyl acetate (4:1), gave 1a as a cloudy oil (1.8 g, 95%).
  • 17
  • [ 367-27-1 ]
  • [ 116457-91-1 ]
  • (R)-methyl 3-(2,4-difluorophenoxy)-2-(tritylamino)propanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
74% With azodicarboxylic acid bis(2-methoxyethyl) ester; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 2h; To a stirred solution of (R)-methyl3-hydroxy-2-(tritylamino)propanoate (800 mg, 2.2 mmol), 2,4-difluorophenol (370 mg, 2.9 mmol), and triphenylphosphine (760 mg, 2.9 mmol) in THF (15 mL) was added dropwise a solution of bis(2-methoxyethyl) azodicarboxylate (670 mg, 2.9 mmol) in THF (2 mL) at 0 C. The mixture was stirred at room temperature for 2 hrs. The mixture was concentrated, and the residue was diluted with EtOAc (50 mL). The diluted mixture was washed with a saturated aqueous NaHC03 solution and then brine, and was dried over Na2S04. After filtration, the filtrate was concentrated. The residue was purified by column chromatography (silica gel, eluted with 3% to 13% EtOAc in hexane) to give the title compound as a colorless gum (771 mg, 74% yield).‘H NMR (300 MHz, CDC13) delta 7.52(6H, d, J = 7.3 Hz), 7.30-7.16 (9H, m), 6.99-6.72 (3H, m), 4.29 (1H, d, J =9.5, 5.2 Hz), 4.02 (1H, dd, J = 9.5, 6.9 Hz), 3.78-3.71 (1H, m), 3.24 (3H, s),2.88 (1H, d, J = 10.3 Hz). MS (ESI)m/z: fragment signal of 243 (positive ion) was observed.
  • 18
  • [ 32315-10-9 ]
  • [ 116457-91-1 ]
  • methyl (4R)-2-oxo-3-(triphenylmethyl)-1,3-oxazolidine-4-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
74% With triethylamine; In toluene; at -5 - 20℃; for 0.5h;Inert atmosphere; A solution of methyl N-(triphenylmethyl)-D-serinate (90.0 g, 249 mmol) and TEA (69.8 g, 690 mmol) in PhMe (1.8 L) was added dropwise to a solution of triphosgene (69.8 g, 41.5 mmol) in PhMe (300 ml_) under an atmosphere of N2, maintaining the temperature at -5 - 10 C (internal). The mixture was stirred at ambient temperature for 30 min. TLC analysis (1 :2 EtOAc/petroleum ether) showed consumption of the starting material. The reaction was quenched by dropwise addition of 1 N HCI (600 mL) and the mixture was stirred for 10 min. The layers were separated. The aqueous layer was basified to pH ~8-9 by addition of 2 N NaOH and then extracted with DCM/PhMe (1 :5, 1.5 L). The combined organic layers were washed with saturated aqueous NaHC03 (500 mL) and brine (500 mL), dried over Na2S04, filtered, and concentrated. The solids were slurried in EtOAc/petroleum ether (1 :3, 400 mL) at room temperature for 30 min. The solids were collected by filtration and dried under vacuum to provide methyl (4R)-2-oxo-3-(triphenylmethyl)-1,3-oxazolidine-4-carboxylate (71 g, 74% yield) as a white solid. NMR (400 MHz, CDCI3) d 7.38 - 7.27 (m, 15H), 4.61 - 4.50 (m, 1H), 4.50 - 4.38 (m, 1H), 4.21 (dd, J=3.3, 8.9 Hz, 1H), 3.49 (s, 3H).
  • 19
  • [ 116457-91-1 ]
  • (4S)-4-(hydroxymethyl)-3-(triphenylmethyl)-1,3-oxazolidin-2-one [ No CAS ]
  • 20
  • [ 116457-91-1 ]
  • (4R)-4-(fluoromethyl)-3-(triphenylmethyl)-1,3-oxazolidin-2-one [ No CAS ]
  • 21
  • 8-chloro-2-[2-hydroxy-4-(trifluoromethyl)phenyl]chroman-4-one [ No CAS ]
  • [ 116457-91-1 ]
  • methyl (2R)-2-amino-3-[2-(8-chloro-4-oxochroman-2-yl)-5-(trifluoromethyl)phenoxy] propanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
1200 mg To a solution of 8-chloro-2-[2-hydroxy-4-(trifluoromethyl)phenyl]chroman-4-one (948.18 mg, 2.77 mmol), methyl (2i?)-3-hydroxy-2-(tritylamino)propanoate (1000.0 mg, 2.77 mmol) and triphenylphosphine (1088.55 mg, 4.15 mmol) in THF (25 mL) was added DIAD (839.21 mg, 4.15 mmol) and the mixture was stirred at r.t. for 16 hours. The mixture was then diluted with water (30 mL) and extracted with EtOAc (30 mL) three times. The combined organic layer was washed with 1 N HC1 (20 mL), brine (20 mL), dried over NaiSCE and concentrated in vacuo.The residue was dissolved in DCM (20 mL) and to the resulting solution was added TFA (3 mL). The mixture was stirred at r.t. for 2 hours. After the reaction was completed, the mixture was concentrated in vacuo and the residue was purified by column chromatography on silica gel (eluent with DCM : MeOH = 20:1 to 10:1) to give methyl (2R)-2-amino-3-[2-(8-chloro-4-oxo- chroman-2-yl)-5-(trifluoromethyl)phenoxy]propanoate (1200 mg, 63.21% yield) as a light yellow solid. MS obsd. (ESI+)[(M+H)+]: 444.1.
  • 22
  • [ 116457-91-1 ]
  • C51H63NO [ No CAS ]
  • 23
  • [ 116457-91-1 ]
  • C39H27F12NO [ No CAS ]
  • 24
  • [ 116457-91-1 ]
  • (R)-2-(methoxydiphenylmethyl)-1-tritylaziridine [ No CAS ]
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