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Type
HazMat fee for 500 gram (Estimated)
Excepted Quantity
USD 0.00
Limited Quantity
USD 15-60
Inaccessible (Haz class 6.1), Domestic
USD 80+
Inaccessible (Haz class 6.1), International
USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic
USD 100+
Accessible (Haz class 3, 4, 5 or 8), International
USD 200+
Structure of 823-78-9 * Storage: {[proInfo.prStorage]}
* 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.
Reference：
[1] Synthesis, 2008, # 24, p. 3937 - 3940
2
[ 7791-25-5 ]
[ 591-17-3 ]
[ 94-36-0 ]
[ 823-78-9 ]
[ 620-20-2 ]
[ 932-77-4 ]
Reference：
[1] Journal of the American Chemical Society, 1951, vol. 73, p. 2940
3
[ 591-17-3 ]
[ 823-78-9 ]
Yield
Reaction Conditions
Operation in experiment
75%
With N-Bromosuccinimide; tetrachlorosilane In acetonitrile at 20℃; for 8 h;
General procedure: To a mixture of NXS and substrate (1 or 6) in CH3CN at room temperature was added SiCl4 and the mixture left to stir until TLC showed the disappearance of the starting material. The reaction was then poured onto H2O and the mixture extracted with CH2Cl2. The extracts were combined, dried over MgSO4 and evaporated. The residue was purified by recrystallization (pet. ether-Et2O, 3:1) to give pure 2b-2g, 3b, or by silica gel column chromatography (hexane-EtOAc 10:1 or 30:1) to give pure 2a,h,i, 3a-5 or 7-9, respectively
62.5%
With N-Bromosuccinimide; dibenzoyl peroxide In tetrachloromethane for 3 h; Heating / reflux
A mixture of 3-bromotoluene (42.8 g, 0.25 mol), N-bromosuccinimide (48.9 g, 0.275 mol) and benzoyl peroxide (0.75 g) in tetrachloromethane (500 mL) was stirred and heated to reflux for 3 h. The mixture was left to stand overnight at laboratory temperature, the solid was filtered off, washed with tetrachloromethane and the filtrates were evaporated. The residue was distilled in vacuo to yield 52.7 g (62.5percent) of 1-bromo-3-bromomethylbenzene, b.p. 135-140° C./1.6 kPa.
62.5%
With N-Bromosuccinimide; dibenzoyl peroxide In tetrachloromethane at 20℃; Heating / reflux
Example 1; {4-[2-(2-Bromo-10,11-dihydro-dibenzo [a,d]cyclohepten-5-ylidene)-ethylsu Ifanyl]-2-methyl- phenoxy} -acetic acid; A mixture of 3-bromotoluene (42.8 g, 0,25 mol), N-bromosuccinimide (48.9 g, 0.275 mol) and benzoyl peroxide (0.75 g) in tetrachloromethane (500 mL) was stirred and heated to reflux for 3 h. The mixture was left to stand overnight at laboratory temperature, the solid was filtered off, washed with tetrachloromethane and the filtrates were evaporated. The residue was distilled in vacuo to yield 52.7 g (62.5 percent) of 1-bromo-3-bromomethylbenzene, b. p. 135- 140 ° C/1.6 kPa.
Reference：
[1] Journal of Organic Chemistry, 2014, vol. 79, # 1, p. 223 - 229
[2] Synthetic Communications, 2010, vol. 40, # 7, p. 998 - 1003
[3] Tetrahedron Letters, 2011, vol. 52, # 31, p. 4026 - 4029
[4] Patent: US2009/12171, 2009, A1, . Location in patent: Page/Page column 11
[5] Patent: WO2005/105736, 2005, A1, . Location in patent: Page/Page column 28
[6] Organic Letters, 2012, vol. 14, # 9, p. 2414 - 2417
[7] Journal of the American Chemical Society, 1951, vol. 73, p. 2940
[8] Journal of the Chemical Society, 1926, p. 220
[9] Journal of the American Chemical Society, 1948, vol. 70, p. 2310,2313
[10] Journal of the American Chemical Society, 1961, vol. 83, p. 943 - 949
[11] Tetrahedron Letters, 1996, vol. 37, # 42, p. 7611 - 7614
[12] Acta Crystallographica Section C: Crystal Structure Communications, 2003, vol. 59, # 4, p. o216-o218
[13] Journal of Organic Chemistry, 2007, vol. 72, # 4, p. 1073 - 1087
[14] Patent: US6586633, 2003, B1,
[15] Helvetica Chimica Acta, 2009, vol. 92, # 3, p. 555 - 566
[16] Journal of Medicinal Chemistry, 2013, vol. 56, # 6, p. 2556 - 2567
[17] Organic Letters, 2013, vol. 15, # 16, p. 4194 - 4197
[18] European Journal of Organic Chemistry, 2014, vol. 2014, # 16, p. 3402 - 3410
4
[ 15852-73-0 ]
[ 823-78-9 ]
Reference：
[1] Organic Process Research and Development, 2002, vol. 6, # 2, p. 190 - 191
[2] Organic Letters, 2018, vol. 20, # 10, p. 3061 - 3064
[3] Organic Letters, 2008, vol. 10, # 11, p. 2143 - 2145
[4] Journal of the American Chemical Society, 2015, vol. 137, # 30, p. 9567 - 9570
Reference：
[1] Journal of Organometallic Chemistry, 1994, vol. 473, # 1-2, p. 71 - 84
9
[ 7791-25-5 ]
[ 591-17-3 ]
[ 94-36-0 ]
[ 823-78-9 ]
[ 620-20-2 ]
[ 932-77-4 ]
Reference：
[1] Journal of the American Chemical Society, 1951, vol. 73, p. 2940
10
[ 71323-99-4 ]
[ 823-78-9 ]
[ 4885-18-1 ]
Reference：
[1] Journal of the Chemical Society, 1929, p. 446
11
[ 56-23-5 ]
[ 128-08-5 ]
[ 78-67-1 ]
[ 591-17-3 ]
[ 823-78-9 ]
Reference：
[1] Proceedings of the Koninklijke Nederlandse Akademie van Wetenschappen, Series B: Physical Sciences, 1953, vol. <B> 56, p. 75,78
12
[ 56-23-5 ]
[ 78-67-1 ]
[ 591-17-3 ]
[ 7726-95-6 ]
[ 823-78-9 ]
Reference：
[1] Proceedings of the Koninklijke Nederlandse Akademie van Wetenschappen, Series B: Physical Sciences, 1953, vol. <B> 56, p. 75,78
13
[ 506-68-3 ]
[ 876476-08-3 ]
[ 823-78-9 ]
Reference：
[1] Justus Liebigs Annalen der Chemie, 1933, vol. 507, p. 1,9
14
[ 506-68-3 ]
[ 823-78-9 ]
Reference：
[1] Justus Liebigs Annalen der Chemie, 1933, vol. 507, p. 1,9
15
[ 506-68-3 ]
[ 857825-62-8 ]
[ 823-78-9 ]
Reference：
[1] Justus Liebigs Annalen der Chemie, 1933, vol. 507, p. 1,9
16
[ 823-78-9 ]
[ 15852-73-0 ]
Reference：
[1] Journal of the American Chemical Society, 1948, vol. 70, p. 4177
[2] Synthetic Communications, 2011, vol. 41, # 18, p. 2712 - 2718
17
[ 823-78-9 ]
[ 35287-42-4 ]
Reference：
[1] Journal of the American Chemical Society, 2014, vol. 136, # 26, p. 9308 - 9319
18
[ 823-78-9 ]
[ 35287-42-4 ]
[ 142906-81-8 ]
Reference：
[1] Journal of Heterocyclic Chemistry, 1992, vol. 29, # 2, p. 335 - 341
19
[ 823-78-9 ]
[ 10269-01-9 ]
Reference：
[1] Journal of the Chemical Society, 1932, p. 696,703
[2] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 14, p. 3720 - 3731
20
[ 823-78-9 ]
[ 4885-18-1 ]
Yield
Reaction Conditions
Operation in experiment
80%
With dimethyl amine In benzene
(i) Dimethylamine (51.4 g, 1.14 mol) was reacted with 3-bromobenzyl bromide (95 g, 0.38 mol) in benzene at 5° and the mixtue was acidified with hydrochloric acid and the mixture was extracted with aqueous 3N hydrochloric acid. The aqueous extracts were made alkaline with aqueous potassium hydroxide and the oil which separated out was distilled to give 3-bromo-N,N-dimethylbenzylamine (65 g, 80percent) b.p. 118°/20 mmHg.
Reference：
[1] Patent: US4496567, 1985, A,
21
[ 823-78-9 ]
[ 124-40-3 ]
[ 4885-18-1 ]
Reference：
[1] Journal of Heterocyclic Chemistry, 1989, vol. 26, p. 1325 - 1330
[2] Journal of the Chemical Society, 1930, p. 2107,2112
[3] Archiv der Pharmazie, 1962, vol. 295 /67, p. 690 - 697
[4] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 15, p. 3993 - 3997
[5] Journal of the American Chemical Society, 2015, vol. 137, # 18, p. 5887 - 5890
22
[ 100-97-0 ]
[ 823-78-9 ]
[ 4885-18-1 ]
Reference：
[1] Journal of the Chemical Society, 1930, p. 2107,2112
23
[ 71323-99-4 ]
[ 823-78-9 ]
[ 4885-18-1 ]
Reference：
[1] Journal of the Chemical Society, 1929, p. 446
24
[ 823-78-9 ]
[ 32194-76-6 ]
Reference：
[1] Journal of the Chemical Society, 1954, p. 2819,2824
[2] Journal of the Chemical Society, 1954, p. 2819,2824
25
[ 823-78-9 ]
[ 30163-20-3 ]
Reference：
[1] Journal of Medicinal Chemistry, 2005, vol. 48, # 21, p. 6607 - 6619
[2] Journal of medicinal chemistry, 1967, vol. 10, # 1, p. 64 - 66
26
[ 823-78-9 ]
[ 28286-79-5 ]
Reference：
[1] Journal of the American Chemical Society, 1948, vol. 70, p. 4177
27
[ 823-78-9 ]
[ 67344-77-8 ]
Yield
Reaction Conditions
Operation in experiment
63.2%
With hydrogenchloride; triethylamine In methanol; methylamine
Referential Example 3 Production of N-(3-Bromobenzyl)methylamine Triethylamine (19.2 g; 100.5 mmol) was dissolved in 40percent solution of methylamine in methanol (150 ml). While the resultant solution was stirred in an ice bath, a solution of 3-bromobenzylbromide (25.1 g; 100.5 mmol) in methanol (40 ml) was added dropwise. After completion of the addition, the mixture was removed from the ice bath, and stirred for 15 hours at room temperature. Methanol and excess methylamine were evaporated under reduced pressure, and the residue was taken up in a mixture of ether and 2N hydrochloric acid (100 ml-100 ml). The aqueous layer was alkalinized with aqueous sodium hydroxide solution, and the mixture was extracted with chloroform (100 ml). The organic layer was washed with saturated aqueous sodium bicarbonate solution and with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, to thereby yield 12.7 g of the target compound as a yellow-orange oily substance (yield: 63.2percent). 1H-NMR (CDCl3, ppm); 2.44 (3H, s), 3.72 (2H, s), 7.16~7.26 (2H, m), 7.38 (1H, m), 7.49 (1H, s).
Reference：
[1] Patent: US6586633, 2003, B1,
28
[ 823-78-9 ]
[ 74-89-5 ]
[ 67344-77-8 ]
Reference：
[1] Journal of Medicinal Chemistry, 1986, vol. 29, # 1, p. 40 - 44
[2] Justus Liebigs Annalen der Chemie, 1933, vol. 507, p. 1,9
29
[ 823-78-9 ]
[ 171663-13-1 ]
Reference：
[1] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 14, p. 3720 - 3731
A pressure tube was charged with diethyl 2-acetamidomalonate(1.74 g, 8.00 mmol) and NaOEt (2.59 g,8.00 mmol), then anhydrous EtOH (10 ml) was added andlight-yellow suspension formed. A solution of m-bromo-benzyl bromide (1) (2.00 g, 8.00 mmol) in anhydrousEtOH (10 ml) was added, and the resulting orange solutionwas heated at 85C for 16 h. After cooling to roomtemperature, orange suspension was concentrated underreduced pressure and the residue was partitioned betweenEtOAc (50 ml) and H2O (50 ml). Water phase wasextracted with EtOAc (3×50 ml), combined extracts werewashed with brine, dried over Na2SO4, and evaporatedunder reduced pressure. The residue was purified bycolumn chromatography on silica gel (100 g), eluenthexane-EtOAc, gradient from 10 to 100% EtOAc. Yield2.76 g (89%), light-yellow solid. Analytical data of thecompound were identical to the literature data.13
9-fluorenyl-methoxycarbonyl-cyclohexyl alanine[ No CAS ]
[ 462-94-2 ]
[ 1458-98-6 ]
[ 78-77-3 ]
[ 1809-10-5 ]
[ 110-53-2 ]
[ 592-55-2 ]
[ 7328-91-8 ]
[ 871-76-1 ]
[ 105-83-9 ]
[ 144-48-9 ]
[ 929-59-9 ]
[ 107-59-5 ]
[ 5324-30-1 ]
[ 5428-54-6 ]
[ 27129-86-8 ]
[ 2417-72-3 ]
[ 2581-34-2 ]
[ 554-84-7 ]
[ 3385-21-5 ]
[ 126-38-5 ]
[ 636-93-1 ]
[ 88-30-2 ]
[ 620-13-3 ]
[ 823-78-9 ]
[ 5035-82-5 ]
[ 29022-11-5 ]
[ 539-48-0 ]
[ 35661-39-3 ]
[ 26759-46-6 ]
[ 20439-47-8 ]
[ 2615-25-0 ]
[ 6393-01-7 ]
[ 5372-81-6 ]
[ 35661-40-6 ]
[ 100-39-0 ]
[ 611-17-6 ]
[ 23915-07-3 ]
[ 71989-23-6 ]
[ 35737-15-6 ]
[ 2592-95-2 ]
[ 18880-00-7 ]
[ 88681-68-9 ]
[ 100063-22-7 ]
[ 75-03-6 ]
[ 106-94-5 ]
[ 104-81-4 ]
[ 589-10-6 ]
[ 107-15-3 ]
[ 109-76-2 ]
[ 110-60-1 ]
[ 7051-34-5 ]
[ 106-95-6 ]
[ 622-95-7 ]
[ 589-15-1 ]
[ 134-20-3 ]
[ 2550-36-9 ]
[ 89-92-9 ]
[ 456-41-7 ]
[ 766-80-3 ]
[ 459-46-1 ]
[ 874-98-6 ]
[ 402-49-3 ]
[ 870-63-3 ]
[ 85118-01-0 ]
[ 22115-41-9 ]
[ 3958-57-4 ]
[ 100-11-8 ]
[ 107-82-4 ]
[ 6482-24-2 ]
[ 3132-64-7 ]
[ 112883-41-7 ]
[ 3433-80-5 ]
[ 52727-57-8 ]
C18H15N2O3PolS[ No CAS ]
C20H20N3OPolS[ No CAS ]
C23H19N2O2PolS[ No CAS ]
C18H23ClN3OPolS[ No CAS ]
C22H26N3OPolS[ No CAS ]
C22H23N2O5PolS[ No CAS ]
C20H26ClN2O3PolS[ No CAS ]
C23H22ClN2O3PolS[ No CAS ]
C20H21FN3O3PolS[ No CAS ]
C22H29N2O3PolS[ No CAS ]
C21H28N3O3PolS[ No CAS ]
C19H26N3O4PolS2[ No CAS ]
C22H30N3OPolS[ No CAS ]
C21H28N3O4PolS[ No CAS ]
C26H26N3OPolS[ No CAS ]
C23H15ClF3N2O2PolS[ No CAS ]
C24H22N3O3PolS[ No CAS ]
C23H16ClF2N2O2PolS[ No CAS ]
C22H22Br2N3OPolS[ No CAS ]
C24H26FN2O5PolS[ No CAS ]
C25H22FN2O4PolS[ No CAS ]
C26H22N3O4PolS[ No CAS ]
C25H25ClN3O3PolS[ No CAS ]
C25H18ClF2N2O3PolS[ No CAS ]
C29H26N3O3PolS[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With piperidine; Carbonyldiimidazole; tin-2-ethylhexanoate dihydrate; potassium tert-butylate; water; N-ethyl-N,N-diisopropylamine; trifluoroacetic acid; diisopropyl-carbodiimide; dibromotriphenylphosphorane; In DMF (N,N-dimethyl-formamide); dichloromethane; N,N-dimethyl acetamide; 1,2-dichloro-ethane;Combinatorial reaction / High throughput screening (HTS);
EXAMPLE 1 [0213] This example shows the synthesis of a combinatorial library of thioquinazolinone derivatives. [0214] Step 1a: Preparation of Wang Bromide Resin [0215] 40 tea bags containing 2 g each of Wang resin (80 g, 120 mmol) was taken in a 5 L PP container. A solution of triphenylphosphine dibromide (152 g, 0.15 M, 3 eq., 360 mmol) in 2000 ml DCM was added and the solution was shaken at room temperature overnight. The resin was sequentially washed with DCM (4×, 1.5 L each) and diethylether (6×, 1.5 L each) and dried under vacuum, to give the bromo wang resin. [0216] Step 1b: Loading of the Nitrophenol on Bromo Wang [0217] 20 g of the Bromo wang resin (1.5 meq/g) was taken in a 2 L wide-mouthed glass container and 1000 mL DMA was addded to it followed by the addition of the nitro phenol (10 eq., 0.3M, 300 mmol). Potasium t-butoxide (33.46 g, 10 eq., 300 mmol) was then added to it and the bottles were heated at 50 C. overnight. The bags were washed alternatively with DMF (500 mL) and DCM (500 mL) 3 cycles followed by 6 cycles of MeOH (500 mL). The tea bags were then dried overnight in air. The following nitrophenols were used: [0218] 2-METHYL-5-NITROPHENOL [0219] 5-HYDROXY-2-NITROBENZOTRIFLUORIDE [0220] 3-METHYL-4-NITROPHENOL [0221] 2-METHOXY-5-NITROPHENOL [0222] M-NITROPHENOL [0223] Step 1c: Reduction of the Nitro Group to Amine [0224] A 2.0 M solution of tin-2-ethylhexanoate dihydrate was prepared in DMF containing 0.5% H2O. The tea bags were added and the solution is heated at 50 C. for 40 hours. After cooling the bags are washed with DMF/10% HOAc (3×), DMF (3×), 5% DIEA/DCM (2×), DCM (2×) and MeOH (2×) and dried in air overnight. [0225] Step 1d: Coupling N-FMOC Protected Amino Acid to Wang Resin. [0226] 20 g of Wang resin (1.5 meq/g) was placed in a porous polypropylene packet (Tea-bag, 60 mm×60 mm, 65mu) and taken in a 1000 mL plastic bottle. DMF (300 mL), DCM (300 mL), FMOC-Cyclohexyl alanine (70.82 g, 6 eq., 0.3M, 180 mmol), DIC (22.71 g, 6 eq., 180 mmol), HOBt (24.32 g, 6 eq., 180 mmol) were added sequentially. After shaking for 12 hours, the packet was washed alternatively with DMF (500 mL) and DCM (500 mL) 3 cycles followed by 6 cycles of MeOH (500 mL). The packet was then dried overnight in air. The tea bags containing the amino acids were then treated with 20% piperidine/DMF for 2 h at room temperature to deblock the FMOC group. The following amino acids were used: [0227] FMOC-GLY-OH [0228] FMOC-ALA-OH [0229] FMOC-L-ISOLEUCINE [0230] FMOC-L-PHENYLALANINE [0231] FMOC-D-NLE-OH [0232] FMOC-CHA-OH [0233] FMOC-L-TRYPTOPHAN [0234] Step 1e: Coupling of the Diamines to Wang Resin [0235] 20 g of Wang resin (1.5 meq/g) was placed in a porous polypropylene packet (Tea-bag, 60 mm×60 mm, 65mu) and taken in a 1000 mL Nalgene bottle. 600 mL of DCM was added followed by the addition of the carbonyl diimidazole (29.9 g, 6 eq., 0.3M, 180 mmol) and the flasks were shaken at room temperature for 3 hours after which they were decanted and washed with DCM (2×, 600 mL). To these Nalgene bottles were added the diamines (6 eq., 0.4M, 180 mmol) in 450 mL of DCM (0.4M) and they were shaken at room temperature overnight. The diamines used were as follows: [0236] 2,2-DIMETHYL-1,3-PROPANEDIAMINE [0237] 1,3-CYCLOHEXANEDIAMINE [0238] (1R,2R)-(-)-1,2-DIAMINOCYCLOHEXANE [0239] TRANS-1,4-DIAMINOCYCLOHEXANE [0240] P-XYLYLENEDIAMINE [0241] 1,4-BIS(3-AMINOPROPYL)PIPERAZINE [0242] ETHYLENEDIAMINE [0243] 1,3-DIAMINOPROPANE [0244] 1,8-DIAMINO-3,6-DIOXAOCTANE [0245] 1,4-DIAMINOBUTANE [0246] 1,5-DIAMINOPENTANE [0247] 1,6-HEXANEDIAMINE [0248] N,N-BIS(3-AMINOPROPYL)METHYLAMINE [0249] 2,2'-THIOBIS(ETHYLAMINE) [0250] 2,5-DIMETHYL-1,4-PHENYLENEDIAMINE [0251] After shaking overnight, the packets was washed alternatively with DMF (500 mL) and DCM (500 mL) 3 cycles followed by 6 cycles of MeOH (500 mL). The packet was then dried in air. [0252] Step 2: Formation of the Isothiocyanate [0253] The o-amino benzoate ester (136 g, 10 eq., 900 mmol) was taken in a 5 L wide-mouthed glass bottle and 2.7 L of dichloroethane was added to it (0.3M). The following esters were used: [0254] METHYL ANTHRANILATE [0255] METHYL 2-AMINO-4-CHLOROBENZOATE [0256] 2-AMINO-4,5-DIMETHOXYBENZOIC ACID [0257] METHYL ESTER [0258] METHYL 3,4,5-TRIMETHOXYANTHRANILATE [0259] DIMETHYL AMINOTEREPHTHALATE [0260] METHYL 2-AMINO-5-BROMOBENZOATE [0261] METHYL 3-AMINOTHIOPHENE-2-CARBOXYLATE [0262] METHYL 3-AMINO-5-PHENYLTHIOPHENE-2-CARBOXYLATE [0263] Thiocarbonyl diimidazole (160 g, 10 eq., 900 mmol) was added to it and the solution was heated at 55 C. overnight to form the isothiocyanate. [0264] Step 3: Formation of the Thioquinazolinone [0265] The next day the tea bags containing the amino acids, diamines and the amino phenols on wang resin (90 mmol) was added to the isothiocyanate solution from reaction 2 and the glass bottles were heated at 55 C. overnight. After cooling the bags was washed alternatively with DMF (2000 mL) and DCM (2000 mL) 3 cycles followed by 6 cycles of MeOH...
With sodium chloride; sodium methylate; In methanol-dimethoxyethane;
Reference Example 1 1-bromo-3-methoxymethylbenzene STR235 To a solution of 3-bromobenzylbromide (15.0 g, 60 mmol) in methanol-dimethoxyethane (DME) (30 ml+10 ml), sodium methylate (4.9 g, 90 mmol) was added under cooling with ice. The solution was stirred at room temperature for 1 hour. The reaction mixture was poured into water. The reaction mixture was extracted with ether. The organic layer was washed with an aqueous saturated solution of sodium chloride, dried over magnesium sulfate. The solvent was distilled off to give the title compound (12.1 g, 100%) having the following physical data. TLC: Rf 0.74 (ethyl acetate:hexane=1:4); NMR: delta 7.50 (s, 1H), 7.42 (dt, J=8, 2 Hz, 1H), 7.3-7.2 (m, 2H), 4.43 (s, 2H), 3.40 (s, 3H).
With sodium chloride; sodium methylate; In methanol-dimethoxyethane;
REFERENCE EXAMPLE 1 1-Bromo-3-Methoxymethylbenzene To a solution of 3-bromobenzyl bromide (15.0 g, 60 mmol) in methanol-dimethoxyethane (DME) (30 ml+10 ml), sodium methylate (4.9 g, 90 mmol) was added under cooling with ice. The mixture was stirred for 1 hour at room temperature. The reaction mixture was poured into water and extracted with ether. The organic layer was washed by an aqueous saturated solution of sodium chloride and dried over magnesium sulfate. The solvent was distilled off to obtain the title compound (12.1 g) having the following physical data. TLC: Rf 0.74 (ethyl acetate:hexane=1:4); NMR (CDCl3): delta 7.50 (s, 1H), 7.42 (dt, J=8, 2 Hz, 1H), 7.3-7.2 (m, 2H), 4.43 (s, 2H), 3.40 (s, 3H).
With sodium chloride; sodium methylate; In methanoldimethoxyethane;
Reference Example 1 1-bromo-3-methoxymethylbenzene To a solution of 3-bromobenzylbromide (15.0 g) in methanoldimethoxyethane (30 ml + 10 ml) was added sodium methylate (4.9 g) under cooling with ice and the mixture was stirred for 1 hour at room temperature. The reaction mixture was poured into water. The reaction mixture was extracted with ether. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and the solvent was evaporated to give the title compound (12.1 g) having the following physical data. TLC: Rf 0.74 (ethyl acetate: hexane = 1: 4); NMR(CDCl3): delta 7.50 (s, 1H), 7.42 (dt, J=8, 2 Hz, 1H), 7.3-7.2 (m, 2H), 4.43 (s, 2H), 3.40 (s, 3H).
With hydrogenchloride; triethylamine; In methanol; methylamine;
Referential Example 3 Production of N-(3-Bromobenzyl)methylamine Triethylamine (19.2 g; 100.5 mmol) was dissolved in 40percent solution of methylamine in methanol (150 ml). While the resultant solution was stirred in an ice bath, a solution of 3-bromobenzylbromide (25.1 g; 100.5 mmol) in methanol (40 ml) was added dropwise. After completion of the addition, the mixture was removed from the ice bath, and stirred for 15 hours at room temperature. Methanol and excess methylamine were evaporated under reduced pressure, and the residue was taken up in a mixture of ether and 2N hydrochloric acid (100 ml-100 ml). The aqueous layer was alkalinized with aqueous sodium hydroxide solution, and the mixture was extracted with chloroform (100 ml). The organic layer was washed with saturated aqueous sodium bicarbonate solution and with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, to thereby yield 12.7 g of the target compound as a yellow-orange oily substance (yield: 63.2percent). 1H-NMR (CDCl3, ppm); 2.44 (3H, s), 3.72 (2H, s), 7.16~7.26 (2H, m), 7.38 (1H, m), 7.49 (1H, s).
With caesium carbonate; In N,N-dimethyl-formamide;
EXAMPLE 1 4-(3-Bromobenzyloxy)-3,5-diiodo-benzoic Acid 3-bromobenzyl Ester A suspension of <strong>[618-76-8]3,5-diiodo-4-hydroxybenzoic acid</strong> (0.39 g, 1.0 mmol), 3-bromobenzyl bromide (0.62 g, 2.5 mmol), and cesium carbonate (0.98 g, 3.0 mmol) in 10 mL DMF was stirred for 15 hours at room temperature. The mixture was then poured into 1 M HCl (100 mL) and a white precipitate formed. The precipitate was isolated by vacuum filtration and was recrystallized from hot isopropanol/chloroform, yielding the title compound as bright white crystals (610 mg, 84%); 1H NMR (CDCl3) delta 8.48 (s, 2H), 7.80 (br. s, 1H), 7.58-7.49 (m, 4H), 7.38-7.28 (m, 3H), 5.31 (s, 2H), 5.01 (s, 2H).
84%
With caesium carbonate; In N,N-dimethyl-formamide;
EXAMPLE 1 Synthesis of 4-(3-Bromo-benzyloxy)-3,5-diiodo-benzoic Acid 3-Bromo-benzyl Ester A suspension of <strong>[618-76-8]3,5-diiodo-4-hydroxybenzoic acid</strong> (0.39 g, 1.0 mmol), 3-bromobenzyl bromide (0.62 g, 2.5 mmol), and cesium carbonate (0.98 g, 3.0 mmol) in 10 mL DMF was stirred for 15 hours at room temperature. The mixture was then poured into 1 M HCl (100 mL) and a white precipitate formed. The precipitate was isolated by filtration and was recrystallized from hot isopropanol/chloroform, yielding the title compound as bright white crystals (610 mg, 84%). 1H NMR (400 MHz, CDCl3): delta 8.51 (s, 2H), 7.88 (d, J=7.6 Hz, 1H), 7.62 (d, J=8 Hz, 1H), 7.58 (d, J=8.4 Hz, 1H), 7.47-7.34 (m, 3H), 7.26-7.21 (m, 2H), 5.44 (s, 2H), 5.15 (s, 2H). TLC (9:1 Hex:EtOAc), Rf 0.49.
(i) Dimethylamine (51.4 g, 1.14 mol) was reacted with 3-bromobenzyl bromide (95 g, 0.38 mol) in benzene at 5 and the mixtue was acidified with hydrochloric acid and the mixture was extracted with aqueous 3N hydrochloric acid. The aqueous extracts were made alkaline with aqueous potassium hydroxide and the oil which separated out was distilled to give 3-bromo-N,N-dimethylbenzylamine (65 g, 80%) b.p. 118/20 mmHg.
With potassium carbonate; In acetonitrile; at 20℃;
Example 24: 4-(3-Bromo-benzyl)-<strong>[23972-41-0]2-phenyl-morpholine</strong>; 1.877g of 3-Bromobenzyl bromide and Ig of <strong>[23972-41-0]2-Phenyl-morpholin</strong>e in 15mL of acetonitrile were stirred at room temperature and 2.076g of potassium carbonate was added. The reaction was stirred at room temperature overnight. The solution was filtered through Celite and concentrated in vacuo to afford a brown solid. Purification by flash chromatography afforded 1.073g of product. 65% yield ES MS m/z332
With potassium carbonate; In acetone;Heating / reflux;
Example 9 4-(3-Bromo-benzyloxy)-2-(2,6-dioxo-piperidin-3-yl)-isoindole-l,3-dioneStep 1 :[187] To a stirred suspension of 3-hydroxyphthalic acid dimethyl ester (1.3 g, 6.2 mmol) in acetone (30 mL) and potassium carbonate (2.5 g, 18.4 mmol) was added 3- bromobenzyl bromide (1.6 g, 6.4 mmol) and refiuxed overnight. The solvent was evaporated and the residue was partitioned between water (100 mL) and ethyl acetate (150 mL) and washed with water (2 x 100 mL). The combined organic phases was dried, concentrated and purified by flash column chromatography (EtOAc/Hexane) to give 3-(3- bromo-benzyloxy)-phthalic acid dimethyl ester (2.5 g, 109% crude yield). The product was used in the next step without further purification.
With potassium carbonate; In acetone; for 24h;Heating / reflux;
1-(3-bromobenzyl)-3-methylimidazolidine-2-one 1-methylimidazolidine-2-one (type W, commercially available) (2 g, 20 mmol) was dissolved in acetone (100 mL) and potassium carbonate (3 g, 20 mmol) added under constant stirring. 3-bromobenzylbromide (type X, commercially available) (2.5 g, 10 mmol) was added to the mixture and then refluxed for 24 h. Water (500 mL) was then added and extraction occurred with chloroform (3*200 mL). The organic phase was dried (MgSO4), filtered and evaporated to low bulk. The raw product was purified by column chromatography (hexane:ethyl acetate, 3:2). (Yield: 812 mg, 30%) Example 879 was produced from the corresponding compound of type W using the same process for 877.
1. Synthesis of 3-(3-bromobenzyl)-<strong>[169206-55-7]2-oxo-1-oxa-3,8-diazaspiro[4.5]decane-8-carboxylic acid tert-butyl ester</strong> (A6) Sodium hydride (246 mg, 60% dispersion in mineral oil, weight percent) was suspended under a nitrogen atmosphere in DMF (15 mL). Compound A3 (1.5 g, 5.85 mmol) was added thereto and the reaction mixture was stirred for 10 min at RT. 3-Bromobenzyl bromide (1.48 g, 5.91 mmol) was added thereto. The reaction mixture was stirred for 18 h at RT, combined with water and extracted with EtOAc. The combined organic phases were washed with sat. aq. NaCl solution, dried over Na2SO4 and the solvent was removed under a vacuum. The residue was dissolved in a mixture of ether and heptane. After removal of the ether, the desired product 3-(3-bromobenzyl)-<strong>[169206-55-7]2-oxo-1-oxa-3,8-diazaspiro[4.5]decane-8-carboxylic acid tert-butyl ester</strong> (A6) (2.33 g, 93% of theoretical) was obtained as a white solid by filtration.
Under argon, 14.8 ml (105.48 mmol) of diisopropylamine were initially charged in 66 ml of dry THF, and the mixture was cooled to -40 C. 42.2 ml (105.48 mmol) of n-butyllithium solution (2.5 M in hexane) were slowly added dropwise, and the mixture was stirred for 30 min. The reaction solution was then cooled to -78 C., and a solution of 10.0 g (70.32 mmol) of <strong>[87661-20-9]ter<strong>[87661-20-9]t-butyl cyclopropanecarboxylate</strong></strong> in 17 ml of THF were added. After 4 h of stirring at -78 C., a solution of 19.34 g (77.36 mmol) of 3-bromobenzyl bromide in 17 ml of THF was added. Slowly, the reaction mixture was warmed to RT overnight, ammonium chloride solution was then added carefully and the mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried over magnesium sulfate and concentrated under reduced pressure. The crude product was purified by chromatography on 750 g of silica gel (mobile phase cyclohexane/dichloromethane 50:1, then 5:1). This gave 13.3 g (60.7% of theory) of the title compound.GC-MS (method 3): Rt=5.94 min; m/z=256 (M-C4H8)+.1H-NMR (400 MHz, DMSO-d6): delta=7.46 (s, 1H), 7.38 (m, 1H), 7.25 (m, 2H), 2.82 (s, 2H), 1.28 (s, 9H), 1.08 (q, 2H), 0.87 (q, 2H).
60.7%
Example 1Atert-Butyl 1-(3-bromobenzyl)cyclopropanecarboxylate; Under argon, 14.8 ml (105.48 mmol) of diisopropylamine were initially charged in 66 ml of dry THF, and the mixture was cooled to -40 C. 42.2 ml (105.48 mmol) of n-butyllithium solution (2.5 M in hexane) were slowly added dropwise and the mixture was stirred for 30 min. The reaction solution was then cooled to -78 C., and a solution of 10.0 g (70.32 mmol) of <strong>[87661-20-9]ter<strong>[87661-20-9]t-butyl cyclopropanecarboxylate</strong></strong> in 17 ml of THF was added. After 4 h of stirring at -78 C., a solution of 19.34 g (77.36 mmol) of 3-bromobenzyl bromide in 17 ml THF was added. The reaction mixture was slowly warmed to RT overnight, and aqueous ammonium chloride solution was then added carefully and the mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried over magnesium sulphate and concentrated under reduced pressure. The crude product was purified by chromatography on 750 g of silica gel (mobile phase cyclohexane/dichloromethane 50:1, then 5:1). This gave 13.3 g (60.7% of theory) of the title compound.GC-MS (Method 1): Rt=5.94 min; m/z=256 (M-C4H8)+.1H-NMR (400 MHz, DMSO-d6): delta [ppm]=7.46 (s, 1H), 7.38 (m, 1H), 7.25 (m, 2H), 2.82 (s, 2H), 1.28 (s, 9H), 1.08 (q, 2H), 0.87 (q, 2H).
General procedure: To a stirring solution of <strong>[1131-40-4]1-bromo-2,4,6-trimethoxybenzene</strong> 8 (0.29 g, 1.17 mmol) in anhydrous THF (4 mL) at -78 C, n-BuLi (1.00 mL, 1.25 M, 1.25 mmol) was added dropwise over 1 min and stirring was continued until a white precipitate formed (ca. 10-15 min). To this mixture, a solution of ZnCl2 (1.20 mL, 1.00 M in THF, 1.20 mmol), was added dropwise and the resulting clear, colourless solution was stirred at -78 C for 15 min and then slowly warmed to 0 C over 30 min. Neat 4-methoxy-benzyl chloride (12a, 110 muL, 0.81 mmol) was added at 0 C, followed immediately by solid Pd(DPEPhos)Cl2 (7 mg, 1 mol %) and the resulting mixture was warmed to 70 C and stirred for 4 h. The mixture was cooled to room temperature and dilute HCl (2 M, 10 mL) was added, followed by CH2Cl2 (20 mL) and the mixture was rapidly stirred for 10 min. The phases were then separated and the aqueous phase was extracted with CH2Cl2 (2×10 mL). The combined organics were dried (Na2SO4), filtered and concentrated in vacuo. Purification of the yellow residue by silica gel chromatography (CH2Cl2/hexanes 1:1) provided 160 mg (68%) of the title compound as a white powdery solid.
With potassium hydroxide; In ethanol; for 5h;Reflux;
General procedure: Commercially available 6-hydroxy-3,4-dihydro-2(1H)-quinolinone (6) or 7-hydroxy-3,4-dihydro-2(1H)-quinolinone (7) (1.50 mmol) was suspended in ethanol (6 mL) containing KOH (1.66 mmol). The reaction was treated with an appropriately substituted alkyl bromide (1.50 mmol) and heated at reflux for 5 h. The reaction progress was monitored using silica gel TLC with ethyl acetate as mobile phase. Upon completion, the reaction was poured into aqueous NaOH (1%) and the resulting precipitate was collected by filtration. The crude thus obtained was purified by recrystallization from ethanol.
(R)-N-(3-bromobenzyl)-N-methyl-1-(naphthalen-1-yl)ethanamine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With N-ethyl-N,N-diisopropylamine; In acetonitrile; for 2h;Reflux; Inert atmosphere;
General procedure: N-Methyl-1-(naphthalen-1-yl)ethanamine (8) (0.37g, 2.00mmol), N,N-diisopropylethylamine (0.39g, 3.02mmol), 1-(bromomethyl)-4-tert-butylbenzene (0.50g, 2.20mmol) and acetonitrile (5mL) were mixed and stirred at reflux under an N2-atmosphere for 2h. The solvent was then removed at reduced pressure and CH2Cl2 (5mL) was added. The dichloromethane phase was washed with water (5mL) and the water phase was back extracted with CH2Cl2 (3×5mL). The combined organic fractions were dried over Na2SO4, and concentrated in vacuum. The crude product was purified by silica-gel column chromatography. Alternatively, the purification was done by filtration through a short silica-gel column (pentane:EtOAc, 9:1), followed by precipitation as it hydrochloride salt by addition of HCl saturated ether. The solid material was washed with cold pentane. Alternatively, using 8·HCl the reaction was run similarly, but employing a 3-fold excess of N,N-diisopropylethylamine.
With potassium carbonate; In tetrahydrofuran; at 50℃; for 18h;
To a solution of ethyl 5-methyl-lH-l,2,4-triazole-3-carboxylate (1.0 g, 6.44 mmol) and l-bromo-3-(bromomethyl)benzene (1.77 g, 7.08 mmol) in THF (32 mL), K2CO3 (1.78 g, 12.88 mmol) was added. The mixture was stirred at 50°C for 18 h, and then the reaction was filtered under vacuum. The solvent was removed under reduced pressure and the crude product was purified on a Biotage pre-packed silica gel column (EtOAc:Hexane 12percent to 100percent EtOAc) to afford ethyl l-(3- bromobenzyl)-5-methyl-lH-l,2,4-triazole-3-carboxylate (1.25 g, 60percent) as a viscous oil. MS(ES+) Ci3H14BrN302 requires: 323, 325 found: 324, 326 [M+H]+(l :l).
60%
With potassium carbonate; In tetrahydrofuran; at 50℃; for 18h;
To a solution of ethyl 5-methyl-lH-l,2,4-triazole-3-carboxylate (1.0 g, 6.44 mmol) and l-bromo-3-(bromomethyl)benzene (1.77 g, 7.08 mmol) in THF (32 mL), K2CO3 (1.78 g, 12.88 mmol) was added. The mixture was stirred at 50°C for 18 h then filtered. The filtrate was concentrated under reduced pressure and the crude product was purified on a Biotage pre-packed silica gel column with a gradient of 12percent to 100percent EtOAc:Hexanes to afford ethyl l-(3-bromobenzyl)-5-methyl-lH- l,2,4-triazole-3-carboxylate (1.25 g, 60percent) as a viscous oil. MS(ES+) Ci3H14BrN302 requires: 323, 325 found: 324, 326 [M+H]+(l :l).
1-(3-bromobenzyl)-1H-pyrazole-3-carbaldehyde[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
76%
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 14h;
Step 1 : l-(3-Bromobenzyl)- lH-pyrazole-3-carbaldehyde To a solution of pyrazol-3-carbaldehyde (10.0 g, 104 mmol) in DMF (333 mL) was added K2CO3 (43 g, 312 mmol) followed by 3-bromobenzyl bromide (27.3 g, 109 mmol) at rt, and the mixture was stirred for 14 h. The reaction was filtered through a celite pad and the residual solid was rinsed with EtOAc. The filtrate was concentrated in vacuo. To the residue was added water (200 mL) and the mixture was extracted with Hexane:EtOAc (1:1, 200 mLx3). The combined organic layers were dried over Na2SC>4, filtered, and concentrated in vacuo. The residue was purified on silica to provide l-(3- bromobenzyl)-lH-pyrazole-3-carbaldehyde (21.1 g, 76percent) as a colorless solid. LCMS (FA): m/z = 261 A (M+H).
45%
With potassium carbonate; In acetonitrile; at 20℃;
General procedure: A mixture of 1H-imidazole-2-carbaldehyde 40 (200 mg, 2.08 mmol), potassium carbonate (0.8630 g, 6.24 mmol) and 3-(bromomethyl)-1,1'-biphenyl 38 (0.7716 g, 3.12 mmol) in acetonitrile (10 mL) was stirred overnight at room temperature, then the solvent was removed, diluted with water, and extracted with ethyl acetate (3 x 30 mL). The combined organic phases were washed with brine, dried with Na2SO4, filtered, concentrated and purified by silica gel chromatography to afford 44 as a pale yellow solid (527 mg, 97percent).
methyl 2-(2-((3-bromobenzyl)oxy)phenyl)acetate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 18h;Inert atmosphere;
To a DMF (100 mL) suspension of <strong>[22446-37-3]methyl 2-(2-hydroxyphenyl)acetate</strong> (CAS 22446-37- 3) (10 g, 60.2 mmol) and K2C03 (9.56 g, 69.2 mmol) was added 3-bromobenzyl bromide (CAS 823-78-9) (16.54 g, 66.2 mmol). The mixture was stirred at room temperature for 18 hours. The mixture was diluted with EtOAc and water. The organic phase was washed four times with water, once with brine, and then dried over Na2S04 before filtration and evaporation. The resulting title compound was used crude in the next step. MS (ESI+) m/z 334.9, 336.9 (M+H).
m-bromobenzyl (3β)3,23-dihydroxyolean-12-en-28-oate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
55%
With potassium carbonate; In N,N-dimethyl-formamide; at 25℃; for 18h;
General procedure: A 25 mL one necked round-bottomed flask was charged with a solution of <strong>[465-99-6]hederagenin</strong> (100 mg, 0.23 mmol) in dry DMF (5 mL),and finely grounded potassium carbonate (1 mmol) was added. To this mixture an alkyl bromide (0.46 mmol) was added, and the reaction was stirred for 18 h at 25 C. The reaction mixture was quenched by adding ethyl acetate (20 mL),washed with an aqueous solution of HCl (5%, 50 mL), followed by brine (50 mL) and dried over Na2SO4. The mixture was filtered, the solvent was removed under reduced pressure in a rotary evaporator, and the crude product was obtained as a yellow solid. This solid was purified bysilica gel column chromatography eluting with hexane/ethyl acetate(3:1 v/v) to afford the pure product as a solid. All yields and physical and spectroscopic data for the compounds are included in the Supplementary Material.
With triethylamine; In tetrahydrofuran; at 30℃; for 16h;
To a solution of 1-bromo-3- (bromomethyl) benzene (500 mg, 2.0 mmol) in THF (10 mL) were added thiomorpholine 1, 1-dioxide hydrochloride (513 mg, 2.99 mmol) and triethylamine (834.7 muL, 6.0 mmol) in turn. The mixture was stirred at 30 for 16 h and quenched with water (20 mL) . The resulting mixture was extracted with EtOAc (30 mL × 3) . The combined organic layers were dried over anhydrous Na2SO4and concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with PE/EtOAc (v/v) 2/1 to give a white solid product (440 mg, 72.30) .[1022]MS (ESI, pos. ion) m/z: 306.00 [M+1]+.
With potassium tert-butylate; In N,N-dimethyl-formamide; at 0 - 20℃; for 2h;
General procedure: t-BuOK (0.67 g, 6 mmol) was added to the DMF solution (5 mL) of 13 (0.72 g, 5 mmol) at 0 oC, stirring, then DMF solution (5 mL) of substituted-benyl bromide (5 mmol) was added to the mixture dropwise, which was stirred at room temperature for 2 h. After completion of the reaction, the mixture was poured into ice water (100 mL), followed by extracted and washed according to 3.2.1, the organic layer was dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to get crude product, which was purified by column chromatography with petroleum ether/ethyl acetate (6 : 1) to afford 14b-14d. (14a was commercial available)
tert-butyl {2-[(3-bromobenzyl)(methyl)amino]ethyl}carbamate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
100%
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;
To a solution of 1-bromo-3-(bromomethyl)benzene (21; 570 mg, 2.28 mmol) in DMF (6.0 mL) were added tert-butyl [2-(methylamino)ethyl]carbamate (400 mg, 2.30 mmol) and K2CO3 (630 mg, 4.56 mmol). After being stirred at room temperature overnight, the mixture was concentrated in vacuo. The residue was diluted with saturated NaHCO3 aqueous solution and extracted with CHCl3. The organic layer was dried over Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (CHCl3/MeOH) to afford tert-butyl {2-[(3-bromobenzyl)(methyl)amino]ethyl}carbamate (25; 782 mg, quantitative yield). To a mixture of 25 (500 mg, 1.46 mmol) in DME (5.0 mL)/water (2.0 mL) were added 15 (500 mg, 1.73 mmol), Na2CO3 (463 mg, 4.37 mmol), and Pd(PPh3)4 (55 mg, 0.048 mmol). The mixture was stirred at 80 C overnight. After being cooled to room temperature, the mixture was concentrated in vacuo. The residue was diluted with saturated NaHCO3 aqueous solution and extracted with CHCl3. The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel (CHCl3/MeOH) to afford tert-butyl [2-(methyl[4'-(morpholin-4-yl)biphenyl-3-yl]methyl}amino)ethyl]carbamate. To a solution of tert-butyl [2-(methyl[4'-(morpholin-4-yl)biphenyl-3-yl]methyl}amino)ethyl]carbamate in EtOH (6.0 mL) was added 4 M HCl/EtOAc (3.00 mL, 12.0 mmol). After being stirred at room temperature overnight, the mixture was concentrated in vacuo. The residue was diluted with saturated NaHCO3 aqueous solution, and the mixture was extracted with CHCl3. The organic layer was dried over Na2SO4 and concentrated in vacuo. To a solution of the residue in EtOH was added (2R,3R)-tartaric acid (104 mg, 0.69 mmol). After being stirred at room temperature for 2 h, the mixture was concentrated in vacuo. To the residue was added EtOAc and the resulting precipitate was filtered to give the product (111 mg, 16%).
methyl (R)-1-benzyl-3-(3-bromobenzyl)-4-oxopiperidine-3-carboxylate[ No CAS ]
methyl (S)-1-benzyl-3-(3-bromobenzyl)-4-oxopiperidine-3-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
General procedure: To a 10 mL reaction tube was added <strong>[57611-47-9]methyl 1-benzyl-4-oxopiperidine- 3-carboxylate</strong> 2c (49.5 mg, 0.2 mmol), 50% aq. KOH (112 mg, 1 mmol, 5 eq) and phase transfer catalyst 1k (12.1 mg, 0.02 mmol, 10 mol%) followed by p-xylene (1 mL). After the mixture was stirred at rt for 30 min, BnBr (71.3 uL, 0.6 mmol, 3 eq) was added, and the stirring was continued at rt for additional 12 h (monitored by TLC analysis). The crude product was purified by column flash chromatography (eluting with 20:1 hexane/EtOAc) to afford 3c (256 mg, 76% yield) as colorless transparent liquid.
N-m-bromobenzyl-2,2,6,6-tetramethylpiperidin-4-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
80%
In toluene; at 230℃; for 0.333333h;Microwave irradiation;
General procedure: A G30 glass tube was charged with the 2,2,6,6-tetramethylpiperidin-4-ol 1 ( 1.0 g, 1 equiv.) and the desired allyl or benzyl bromide 2 (0.5 equiv.) dissolved in dry toluene (7.5 mL). Stirring speed and power were respectively fixed at 600 rpm and 230 W. The aqueous layer was extracted 3 times with AcOEt (3x15 mL) and the combined organic phases were washed with water (10 mL), brine (10 mL) and dryed over Na2SO4. After concentration under vacuum, the residue was purified by flash chromatography on silicagel using a combination of petroleum ether and ethyl acetate for benzylic products and dichloromethane and methanol for allylic products to yield the pure desired products.
With tris(bipyridine)ruthenium(II) dichloride hexahydrate; potassium carbonate; triphenylphosphine; In acetonitrile; at 20℃; for 4h;Schlenk technique; Inert atmosphere; Irradiation;
In a Schlenk tube equipped with a magnetic stirrer, 163.2 mg of K2CO3 (1.5:1 molar ratio to m-bromobenzyl bromide) was added, and 314.4 mg of triphenylphosphine (molar ratio to m-bromobenzyl bromide was 1.5:1), 3.8 mg Ru(bpy)3Cl2-6H2O (molar ratio to m-bromobenzyl bromide is 0.005:1), 60 mg paraformaldehyde, 10 mL acetonitrile, 248 mg 3-bromobenzyl bromide, argon gas for 5 minutes Under visible light, normal temperature, reaction time is 4h,The product was isolated and purified by petroleum ether to give 162 mg of 3-bromostyrene (formula 4) in a yield of 89%.
With silver(l) oxide; In n-heptane; dichloromethane; at 60℃;
[00415] To a dry reaction flask was added rapamycin (1.0 g, 1.09 mmol, 1.0 equiv) followed by heptanes (8.7 mL) and DCM (3.4 mL). 3-Bromobenzyl bromide (2.17 g, 8.72 mmol, 8.0 equiv) and silver(I) oxide (3.01 g, 13.0 mmol, 12.0 equiv) were added to the solution and the reaction flask was capped and heated at 60 C until full consumption of rapamycin, as determined by LCMS analysis. The reaction was then cooled to room temperature, diluted with EtOAc (15 mL), filtered through Celite, and concentrated under reduced pressure to provide a yellow solid. Purification by chromatography on silica gel (10?40% EtOAc/heptanes) afforded the product (Intermediate 1 ) as a white solid (788 mg, 67% yield). LCMS (ESI) m/z: [M + Na] calcd for 1104.50; found 1104.5.
General procedure: Compound 1 (10 mmol), anhydrous potassium carbonate (20 mmol, K2CO3) and DMF (20 mL) were added to a 100 mL-dry eggplant flask and stirred at room temperature for 30 min prior to addition of p-bromobenzyl bromide (12 mmol). The resulting mixture was maintained at 80 C for 3-8 h, and the reaction course was monitored using TLC. Upon the reaction completion, the mixture was cooled to room temperature before the addition of 100mL of water, and the system was extracted with ethyl acetate (30 mL 3). The organic phase was dried over anhydrous Na2SO4 and concentrated using rotary evaporator. The crude product 2 was used in the next step without further purification.
With potassium carbonate; In acetonitrile; at 85℃;
General procedure: To a solution of compound 3 (<strong>[51135-91-2]4-amino-2,3-dihydro-1H-inden-1-one</strong>, 1.00 g, 1.0 equiv) and potassium carbonate (1.21 g, 1.1 equiv) in acetonitrile (35 mL) was added bromide derivative (1.1 equiv). The mixture was stirred for 3 h at 85 C. Then, the reaction was cooled to room temperature and the potassium carbonate was filtrated off and washed with saturated saline solution and ethyl acetate (3×15 mL). The combined organic phase was concentrated under vacuo and purified on a silica gel chromatography to give corresponding target product (b1-b6).
1-(3-bromobenzyl)-4-[(5,6-dimethoxy-1-indanone-2-ylidene)methyl]pyridinium bromide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
64%
In acetonitrile; at 80℃; for 48h;
General procedure: 5,6-Dimethoxy-2-[(pyridin-4-yl)methylene)-1-indanone (0.35 mmol) was dissolved in 4 cc acetone (for synthesis of 5a) or acetonitrile (for synthesis of 5b-o) under refux temperature, and then 1.05 mmol of appropriate alkyl halides was added. The reaction mixture was stirred for 48 h under refux condition. The precipitate was fltered and washed with appropriate solvent. The obtained solid was dried under reduced pressure to aford related compounds.
General procedure: The mixture of stirred DTET (100 mg, 0.16 mmol) and NaH (20 mg,0.83 mmol) was dissolved in 2 mL DMF at 0 C. Then, R1Br (0.5 mmol)dissolved in 0.5 mL DMF was added to the DTET solution, and themixture was stirred at 0 C for 6 h, then heated to 92 C until the TLCanalysis showed that the reaction was completed. The temperature ofthe mixture was cooled to room temperature and vacuum evaporated.The residue was purified using aluminum column chromatography, and4a-4 h were obtained using CH2Cl 2/CH3OH as the eluent.
General procedure: The mixture of stirred DTET (100 mg, 0.16 mmol) and NaH (20 mg,0.83 mmol) was dissolved in 2 mL DMF at 0 C. Then, R1Br (0.18 mmol)dissolved in 0.5 mL DMF was added to the DTET solution, and themixture was stirred until the TLC analysis showed that the reaction wascompleted. The temperature of the mixture was cooled to room temperatureand vacuum evaporated. The residue was purified using aluminumcolumn chromatography, and 3a-3m were obtained usingCH2Cl2/CH3OH as the eluent
In N,N-dimethyl-formamide; at 80.0℃; for 24.0h;Inert atmosphere;
General procedure: To a 100 mL of round-bottomed flask charged with a magnetic stirrer bar was added benzylbromide (1.71 g, 10 mmol) in DMF (30 mL). Sodium benzenesulfinate dihydrate (2.40 g, 12 mmol)was added to the solution, and the mixture was stirred at 80 C for 24 h. Saturated 10 mL of NH4Claq. was added to the reaction mixture, and organic and aqueous layers were separated. After theaqueous layer was extracted with EtOAc, combined organic layer was washed with water and brineand dried over MgSO4. The solvents were removed under reduced pressure, and the crude productwas subjected to a flash chromatography (EtOAc/CH2Cl2/hexane, 1:2:7) to afford the desired benzylsulfone in 82% yield (1.90 g).
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