23020-15-7|(1S,2S)-2-Phenylcyclopropanecarboxylic acid| Ambeed

CAS No. :	23020-15-7
Formula :	C₁₀H₁₀O₂
M.W :	162.19
SMILES Code :	O=C([C@@H]1[C@@H](C2=CC=CC=C2)C1)O
MDL No. :	MFCD12195831
InChI Key :	AHDDRJBFJBDEPW-BDAKNGLRSA-N
Pubchem ID :	778517

Safety of [ 23020-15-7 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Application In Synthesis of [ 23020-15-7 ]

* 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 [ 23020-15-7 ]

[ 23020-15-7 ] Synthesis Path-Downstream 1~54

1
[ 908094-01-9 ]
[ 23020-15-7 ]
(1S,2S)-2-phenylcyclopropanecarboxylic acid methyl ester [ No CAS ]

References: [1]Helvetica Chimica Acta,1986,vol. 69,p. 1936 - 1958.
[2]Journal of Organic Chemistry,1978,vol. 43,p. 4447 - 4452.
[3]Tetrahedron,1970,vol. 26,p. 1675 - 1684.
[4]Organic and Biomolecular Chemistry,2006,vol. 4,p. 2777 - 2784.
[5]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 2388 - 2399.

2
[ 23020-15-7 ]
[ 29667-50-3 ]

References: [1]Tetrahedron,1970,vol. 26,p. 1675 - 1684.

3
[ 23020-15-7 ]
(+)-trans-2-Phenylcyclopropyliodid [ No CAS ]

References: [1]Tetrahedron,1970,vol. 26,p. 1675 - 1684.

4
[ 23020-15-7 ]
[ 110659-58-0 ]

References: [1]Bulletin of the Chemical Society of Japan,1981,vol. 54,p. 2151 - 2160.
[2]Journal of Organic Chemistry,1994,vol. 59,p. 7401 - 7409.
[3]Helvetica Chimica Acta,1986,vol. 69,p. 1936 - 1958.
[4]Patent: CN105566262,2016,A .

5
ethyl (S,S)-2-phenylcyclopropane-1-carboxylate [ No CAS ]
[ 23020-15-7 ]

References: [1]Helvetica Chimica Acta,1986,vol. 69,p. 1936 - 1958.
[2]Angewandte Chemie,1992,vol. 104,p. 439 - 441.
[3]Tetrahedron Asymmetry,1996,vol. 7,p. 3505 - 3512.
[4]Journal of Medicinal Chemistry,2016,vol. 59,p. 1501 - 1517.
[5]Angewandte Chemie - International Edition,2016,vol. 55,p. 16110 - 16114.
Angew. Chem.,2016,vol. 128,p. 16344 - 16348.

6
[ 939-90-2 ]
[ 23020-15-7 ]

Yield	Reaction Conditions	Operation in experiment
	With ChiralpakAD 5 u; In ethanol; at 35℃; under 75007.5 Torr;Supercritical conditions; Resolution of racemate;	Preparative supercritical fluid chromatography (SFC) was performed on a Berger Multigram II operating at 50 mL/min at 35 C. and 100 bar backpressure using stacked injections. The column was a ChiralpakAD 5 u, 250×21 mm. The eluent was CO2 (70%) and ethanol (30%).

References: [1]Bulletin of the Chemical Society of Japan,1981,vol. 54,p. 2151 - 2160.
[2]Journal of Medicinal Chemistry,2000,vol. 43,p. 3923 - 3932.
[3]Patent: US2013/12530,2013,A1 .Location in patent: Paragraph 0165.
[4]Patent: WO2014/19023,2014,A1 .
[5]ChemMedChem,2016,p. 1904 - 1914.

7
[ 23020-15-7 ]
[ 222632-77-1 ]
((1S,2S)-2-Phenyl-cyclopropyl)-[(S)-3-(pyrrolidine-1-carbonyl)-3,4-dihydro-1H-isoquinolin-2-yl]-methanone [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,1999,vol. 9,p. 437 - 442.

8
[ 23020-15-7 ]
[ 3721-28-6 ]

References: [1]Tetrahedron Letters,2000,vol. 41,p. 6501 - 6505.
[2]Tetrahedron Asymmetry,1996,vol. 7,p. 3505 - 3512.

9
(+/-)-trans-2-phenylcyclopropanecarbonitrile [ No CAS ]
[ 23020-15-7 ]
[ 928054-81-3 ]
[ 58641-87-5 ]
[ 3471-10-1 ]

References: [1]Tetrahedron Letters,2000,vol. 41,p. 6501 - 6505.
[2]Tetrahedron Letters,2000,vol. 41,p. 6501 - 6505.

10
(+/-)-trans-2-phenylcyclopropanecarbonitrile [ No CAS ]
[ 23020-15-7 ]
[ 58641-87-5 ]
[ 3471-10-1 ]

References: [1]Tetrahedron Letters,2000,vol. 41,p. 6501 - 6505.
[2]Advanced Synthesis and Catalysis,2003,vol. 345,p. 695 - 698.

11
[ 23020-15-7 ]
[ 1013-76-9 ]
[ 307952-37-0 ]

References: [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 3923 - 3932.

12
[ 23020-15-7 ]
[ 1013-78-1 ]
[ 307952-30-3 ]

References: [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 3923 - 3932.

13
[ 131899-86-0 ]
[ 23020-15-7 ]

References: [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 3923 - 3932.

14
rac-(1R,2R)-2-phenylcyclopropanecarboxamide [ No CAS ]
[ 23020-15-7 ]
[ 928054-81-3 ]
[ 58641-87-5 ]
[ 3471-10-1 ]

References: [1]Tetrahedron Asymmetry,2004,vol. 15,p. 347 - 354.
[2]New Journal of Chemistry,2002,vol. 26,p. 1575 - 1583.

15
2-phenyl-cyclopropanecarbonitrile [ No CAS ]
[ 23020-15-7 ]
[ 58641-87-5 ]
[ 3471-10-1 ]

References: [1]New Journal of Chemistry,2002,vol. 26,p. 1575 - 1583.
[2]New Journal of Chemistry,2002,vol. 26,p. 1575 - 1583.

16
(1S)-1-formyl-2-phenylcyclopropane [ No CAS ]
[ 23020-15-7 ]
[ 23020-18-0 ]

References: [1]Journal of Organic Chemistry,2003,vol. 68,p. 9255 - 9262.

17
(+/-)-trans-2-phenylcyclopropanecarbonitrile [ No CAS ]
[ 23020-15-7 ]
[ 58641-87-5 ]
[ 3471-10-1 ]
trans-2-phenylcyclopropanecarbonitrile [ No CAS ]

References: [1]Tetrahedron Asymmetry,2004,vol. 15,p. 347 - 354.

18
[ 23020-15-7 ]
meso-1,2-diphenyl-1,2-diaminoethane [ No CAS ]
(1S,2S)-2-Phenyl-cyclopropanecarboxylic acid (2-amino-1,2-diphenyl-ethyl)-amide [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 435 - 438.

19
[ 23020-15-7 ]
[ 473252-82-3 ]
(4-{2-[Bis-(4-fluoro-phenyl)-methoxy]-ethyl}-piperidin-1-yl)-((1S,2S)-2-phenyl-cyclopropyl)-methanone [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 1766 - 1772.

20
[ 939-90-2 ]
[ 23020-15-7 ]
[ 3471-10-1 ]

Yield	Reaction Conditions	Operation in experiment
	Resolution of racemate;	±trans-2-phenylcyclopropanecarboxylic acid was separated into constituent enantiomers (Intermediate Y and Z) using chiral SFC. Intermediate Y: 1HNMR (300 MHz, CDC13) δ 1HNMR (300 MHz, CDC13) δ 7.35-7.09 (m, 5H), 2.61 (ddd, 1H), 1.91 (dq, 1H), 1.67 (q, 1H), 1.42 (dq, 1H). ESIMS m/z [M-H]+ 161.2. [a]D24 4 -259.546 (c 0.119, MeOH). Absolute stereochemistry assigned by comparison with literature (JMC 2000, p3923; JMC 2011, p957). Intermediate Z: 1HNMR (300 MHz, CDC13) δ 7.35-7.09 (m, 5H), 2.61 (ddd, 1H), 1.91 (dq, J = 4.8, 3.9, 1H), 1.67 (q, 1H), 1.42 (dq, 1H). ESIMS m/z [M-H]+ 161.2. [a]D245 +249.261 (c 0.102, MeOH). Absolute stereochemistry assigned by comparison with literature (JMC 2000, p3923; JMC 2011, p957).

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 5291 - 5301.
[2]Patent: WO2015/191799,2015,A1 .Location in patent: Page/Page column 48.

21
(+/-)-trans-2-phenylcyclopropanecarbonitrile [ No CAS ]
[ 23020-15-7 ]
[ 58641-87-5 ]
[ 3471-10-1 ]

References: [1]New Journal of Chemistry,2002,vol. 26,p. 1575 - 1583.

22
(+/-)-trans-2-phenylcyclopropanecarbonitrile [ No CAS ]
[ 23020-15-7 ]
[ 928054-81-3 ]
[ 58641-87-5 ]
[ 3471-10-1 ]

References: [1]New Journal of Chemistry,2002,vol. 26,p. 1575 - 1583.

23
[ 23020-15-7 ]
trans-(S,S)-4-[2-[bis(4-fluorophenyl)methoxy]ethyl]-1-(2-phenylcyclopropylmethyl)piperidine [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 1766 - 1772.

24
[ 23020-15-7 ]
4,5-Diphenyl-2-((1S,2S)-2-phenyl-cyclopropyl)-4,5-dihydro-1H-imidazole [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 435 - 438.

25
[ 23020-15-7 ]
(1S,2S)-trans-1-[(2-phenylcyclopropyl)methyl]-4-(2,4-dimethylphenyl)piperazine [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 3923 - 3932.

26
[ 23020-15-7 ]
(1S,2S)-trans-1-[(2-phenylcyclopropyl)methyl]-4-(2,4-dichlorophenyl)piperazine [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 3923 - 3932.

27
(1SR,2SR)-2-phenylcyclopropanecarbonyl chloride [ No CAS ]
[ 23020-15-7 ]

References: [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 3923 - 3932.
[2]Patent: WO2014/19023,2014,A1 .

28
(1R,2R)-2-Phenyl-cyclopropanecarboxylic acid ((R)-1-phenyl-ethyl)-amide [ No CAS ]
[ 23020-15-7 ]

References: [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 3923 - 3932.

29
[ 23020-15-7 ]
(1R,2S)-1-amino-2-phenylcyclopropane [ No CAS ]

References: [1]Tetrahedron Asymmetry,1996,vol. 7,p. 3505 - 3512.
[2]Tetrahedron Asymmetry,1996,vol. 7,p. 3505 - 3512.
[3]Angewandte Chemie - International Edition,2016,vol. 55,p. 16110 - 16114.
Angew. Chem.,2016,vol. 128,p. 16344 - 16348.

30
[ 23020-15-7 ]
[ 185256-47-7 ]

References: [1]Tetrahedron Asymmetry,1996,vol. 7,p. 3505 - 3512.
[2]Tetrahedron Asymmetry,1996,vol. 7,p. 3505 - 3512.

31
[ 23020-15-7 ]
(1S,2S)-2-phenylcyclopropane-1-carbaldehyde [ No CAS ]

References: [1]Journal of Organic Chemistry,1994,vol. 59,p. 7401 - 7409.

32
[ 23020-15-7 ]
(1R,2S)-1-(1-propenyl)-2-phenylcyclopropane [ No CAS ]

References: [1]Journal of Organic Chemistry,1994,vol. 59,p. 7401 - 7409.

33
[ 23020-15-7 ]
(+)-trans-1-(o-Methoxycarbonylphenyl)-2-phenylcyclopropan [ No CAS ]

References: [1]Tetrahedron,1970,vol. 26,p. 1675 - 1684.

34
[ 928055-00-9 ]
[ 23020-15-7 ]

Yield	Reaction Conditions	Operation in experiment
	With sulfuric acid; water; In 1,4-dioxane; at 100℃; for 24h;	i) trans-(+)-2-Phenyl-cyclopropanecarboxylic acid; A solution of fcans-(+)-2-phenyl-cyclopropanecarboxylic acid (2-hydroxy-1-phenyl- ethyl)-amide (150 mg, 0.534 mmol) in dioxane (5 mL) was added to 3N H2SO4 (5 mL). The mixture was stirred at 100 C for 24 h and then poured into water and extracted with CH2CI2 (x3). The combined organic phases were dried over MgSO4, EPO <DP n="129"/>filtered and concentrated. and all volatiles were removed under vacuum. The crude residue was purified by silica gel column chromatography using a mixture of EtOAc/hexane (1 :2) as an eluent to afford the title compound as colorless solid (73 mg, 84%). 1H NMR (CDCI3): δ (ppm) 10.3 (br. S, 1 H), 7.34-7.22 (m, 3 H), 7.14 (d, 2 H1 J = 7.0 Hz), 2.64 (m, 1 H), 1.93 (m, 1 H), 1.70 (m, 1 H), 1.44 (m, 1 H). 13C NMR (CDCI3): δ (ppm) 180.2, 139.9, 128.9 (2), 127.1 , 126.7 (2), 27.5, 24.4, 17.9. (+)-CO2H, [α]D +374, c 0.55, CHCI3.

References: [1]ChemMedChem,2016,p. 1904 - 1914.
[2]Journal of Medicinal Chemistry,2009,vol. 52,p. 1885 - 1902.
[3]Patent: WO2007/25144,2007,A1 .Location in patent: Page/Page column 127-128.

35
[ 23020-15-7 ]
[ 78738-39-3 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride;N,N-dimethyl-formamide; In toluene; at 80℃; for 2.5h;	ii) trans-(+)-(2-Phenyl-cyclopropyl)-methylamine hydrochloride; To a solution of /ra/7s-(+)~2-phenyl-cyclopropanecarboxylic acid (60 mg, 0.37 mmol) in toluene (3 ml_) were added dropwise several drops of dimethylformamide and thionyl chloride (0.403 ml_, 5.55 mmol). After stirring at 80 C for 2.5 h, the reaction mixture was concentrated under vacuum. The resulting residue was dissolved in toluene (2 ml_) again, and the solution was added to liquid ammonia (ca. 10 ml_) at - 78 C. After stirring at -78 C for 30 min and then at room temperature for 30 min, CH2CI2 (10 ml) was added to the mixture at -78 C and the resulting mixture was stirred at room temperature overnight. After addition of EtOAc, the mixture was washed with satd. aqueous NH4CI (x2), dried over Na2SO4 and all volatiles were removed under vacuum. The corresponding amide was isolated as pearl yellow powders and further purified by recrystallization from hexane/EtOAc (45 mg).
	With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 20℃; for 0.75h;	To a solution of (l S,2S)-2-phenyl-cyclopropanecarboxylic acid ( 170 mg, 1.05 mmol) in dichloromethane ( 10 ml ) was added oxallyl dichloride ( 145 mg, 1.2 mmol) followed by a few drops of N, N-dimethylformamide at RT. The reaction mixture was stirred at RT for 45 mins before it was concentrated down and dissolved in dichloromethane (1.5 ml). The solution was added slowly to a solution of (S)-l- (4-bromo-phenyl)-propylamine (250 mg, l.Ommol, HC1 salt) and triethylamine (222 mg, 2.2 mmol) in dichloromethane (10 ml) at 0 C. The resulting reaction mixture was stirred at RT for 1.5h. Water was added and the aqueous layer was extracted by dichloromethane. Organic layer was dried by magnesium sulfate and concentrated. The residue was purified via column chromatography on silica gel to afford (1 S,2S)- 2-phenyl-cyclopropanecarboxylic acid [(S)-l-(4-bromo-phenyl)-propyl]-amide (330 mg, 92%). XH NMR (400 MHz, CHLOROF ORM-d) δ ppm 7.37 (d, J=8.6 Hz, 2 H), 7.15 - 7.23 (m, 2 H), 7.11 (d, J=7.3 Hz, 1 H), 7.08 (d, J=8.3 Hz, 2 H), 6.98 (d, J=7.3 Hz, 2 H), 5.75 (d, J=7.6 Hz, 1 H), 4.77 (q, J=7.5 Hz, 1 H), 2.31 - 2.41 (m, 1 H), 1.65 - 1.81 (m, 2 H), 1.48 - 1.59 (m, 2 H), 1.12 - 1.23 (m, 1 H), 0.82 (t, J=7.4 Hz, 3 H); LRMS ( ESI) (M + 1) = 360.04. Molecular Formula =Ci9H20BrNO.
	With oxalyl dichloride; In dichloromethane; at 20℃; for 2.5h;	In a dry 100 ml round-bottomed flask was added oxalyl chloride (2.0 ml, 23 mmol) to 8B (0.25 g, 1.5 mmol) in CH2Cl2 at room temperature to give a yellow solution. In 2.5 hours, the reaction was complete. The crude mixture was concentrated in vacuo and residual <n="164"/>PATENT ASKl -5001 -WOTFA was removed azeotropically with toluene 3 times to give the desired product (lS,2S)-2- phenylcyclopropanecarbonyl chloride (8B-1), which was used in the next step without further purification.

References: [1]Patent: WO2007/25144,2007,A1 .Location in patent: Page/Page column 128.
[2]Journal of Medicinal Chemistry,2009,vol. 52,p. 1885 - 1902.
[3]Patent: WO2011/44195,2011,A1 .Location in patent: Page/Page column 26.
[4]Organic Letters,2013,vol. 15,p. 1350 - 1353.
[5]Patent: WO2009/123986,2009,A1 .Location in patent: Page/Page column 162-163.
[6]Journal of the American Chemical Society,2018,vol. 140,p. 15596 - 15600.

36
[ 105367-36-0 ]
[ 23020-15-7 ]

References: [1]Organic and Biomolecular Chemistry,2006,vol. 4,p. 2777 - 2784.

37
C₁₉H₁₇NO₃ [ No CAS ]
[ 23020-15-7 ]

References: [1]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 2388 - 2399.

38
[ 23020-15-7 ]
[ 4548-34-9 ]

References: [1]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 2388 - 2399.
[2]Angewandte Chemie - International Edition,2016,vol. 55,p. 16110 - 16114.
Angew. Chem.,2016,vol. 128,p. 16344 - 16348.

39
trans-2-phenyl-1-cyclopropanecarboxylic acid [ No CAS ]
[ 23020-15-7 ]
[ 3471-10-1 ]

Yield	Reaction Conditions	Operation in experiment
	With Chiralcel AD-H; In hexane; isopropyl alcohol;Resolution of racemate;Purification / work up;	Enantiomers (R,2R)- and (15',25)-2-phenylcyclopropanecarboxylic acid (8A, and 8B, respectively) were separated from 1 gram of a commercially available racemic mixture on a Waters System using Chiralcel AD-H 250x2 lmm at a flow rate of 20mL/min in 96-4% Hexane:iPrOH. Each injection was 50 mg/mL. Only the first peak was separated out but the second and third peak eluted concurrently. The first peak, (lS,2S)-2- phenylcyclopropanecarboxylic acid (8B), and the third peak, (lR,2R)-2- phenylcyclopropanecarboxylic acid (8A), were in a 1 :1 ratio and composed the majority of mixture. The second peak is the cis diastereomers. The separation yielded 420 mg (41% recovery) for 8B, and 750 mg for the mixture of 8A and cis diastereomers. Optical rotation for the first peak, (15f,25)-2-phenylcyclopropanecarboxylic acid (8B), is +337 (c=0.761, CHCl3).

References: [1]Patent: WO2009/123986,2009,A1 .Location in patent: Page/Page column 161.

40
[ 938462-79-4 ]
[ 23020-15-7 ]
[ 1265913-05-0 ]

References: [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 957 - 969.

41
[ 51596-47-5 ]
[ 23020-15-7 ]
[ 1265913-03-8 ]

References: [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 957 - 969.

42
[ 23020-15-7 ]
[ 1286280-27-0 ]

References: [1]Patent: WO2011/44195,2011,A1 .

43
[ 23020-15-7 ]
[ 917-54-4 ]
[ 196609-07-1 ]

References: [1]Bulletin of the Korean Chemical Society,2011,vol. 32,p. 2076 - 2078.

44
[ 23020-15-7 ]
[ 6148-64-7 ]
[ 1260614-90-1 ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 8838 - 8858,21.

45
((1S)-2-formyl-cyclopropyl)-benzene [ No CAS ]
[ 23020-15-7 ]
[ 48126-51-8 ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 8838 - 8858,21.

46
[ 23020-15-7 ]
[ 883894-57-3 ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 8838 - 8858,21.

47
[ 23020-15-7 ]
[ 883894-58-4 ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 8838 - 8858,21.

48
[ 23020-15-7 ]
[ 1417656-45-1 ]
[ 1417655-74-3 ]

Yield	Reaction Conditions	Operation in experiment
16%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; water; ethyl acetate;	General procedure: (1S,2S)-2-Phenyl-cyclopropanecarboxylic acid [(S)-1-(5-methyl-pyridin-2-yl)ethyl]-amide N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (0.709 g, 3.70 mmol) and 1-hydroxybenzotriazole (0.667 g, 4.93 mmol) were added to a stirred mixture of IM46 (0.60 g, 3.70 mmol) and commercially available (S)-1-(5-methyl-pyridin-2-yl)-ethylamine hydrochloride (Supplier Netchem Inc., Catalog No 528193) (0.426 g, 2.47 mmol) and N,N-diisopropylethylamine (0.859 ml, 4.93 mmol) in THF (25 ml). The solution was stirred at rt overnight. Water was added and the mixture was extracted with EtOAc (3*80 ml). The combined organic phases were washed with brine, dried over MgSO4, filtered and the solvent was evaporated of in vac. The crude product was purified by silica gel chromatography (EtOAc in heptanes 1:1). Yield of Compound 2: 110 mg (16%). LC-MS (m/z) 281.1 (MH+), tR=0.91 min (method A).

References: [1]Patent: US2013/12530,2013,A1 .Location in patent: Paragraph 0232-0233.

49
[ 23020-15-7 ]
[ 1417656-49-5 ]
[ 1417655-94-7 ]

Yield	Reaction Conditions	Operation in experiment
78%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 20℃;	General procedure: N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (0.39 g, 2.03 mmol) and 1-hydroxybenzotriazole (0.366 g, 2.71 mmol) were added to a stirred mixture of IM46 (0.22 g, 1.36 mmol) and commercially available (R)-2-amino-2-(6-trifluoromethyl-pyridin-3-yl)-ethanol hydrochloride (Supplier Netchem Inc., Catalog No 517882) (0.494 g, 2.03 mmol) and N,N-diisopropylethylamine (0.472 ml, 2.71 mmol) in THF (20 ml). The solution was stirred at rt overnight. Water was added and the mixture was extracted with EtOAc (3*80 ml). The combined organic phases were washed with brine, dried over MgSO4, filtered and the solvent was evaporated of in vac. The crude product was purified by silica gel chromatography (EtOAc in heptanes 10:1). Yield of Compound 22475 mg (78%). 1H-NMR (500 MHz, DMSO) δ 8.77 (d, 1H), 8.74 (s, 1H), 8.00 (d, 1H), 7.88 (d, 1H), 7.27 (m, 2H), 7.18 (m, 1H), 7.13 (d, 2H), 5.04 (m, 2H), 3.64 (m, 2H), 2.22 (m, 1H), 2.07 (m, 1H), 1.37 (m, 1H), 1.37 (m, 1H), 1.23 (m, 1H). LC-MS (m/z) 351.1 (MH+), tR=1.51 min (method A).

References: [1]Patent: US2013/12530,2013,A1 .Location in patent: Paragraph 0272-0273.

50
[ 23020-15-7 ]
(R)-2-amino-2-(6-methyl-pyridin-3-yl)-ethanol dihydrochloride [ No CAS ]
[ 1417656-43-9 ]

Yield	Reaction Conditions	Operation in experiment
140 mg	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 20℃;	N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (0.316 g, 1.65 mmol) and 1-hydroxybenzotriazole (0.223 g, 1.65 mmol) were added to a stirred mixture of IM46 (0.18 g, 1.1 mmol) and commercially available (R)-2-Amino-2-(6-methyl-pyridin-3-yl)-ethanol dihydrochloride (Supplier Netchem Inc., Catalog No 549945) (0.128 g, 1.21 mmol) and N,N-diisopropylethylamine (0.575 ml, 3.30 mmol) in THF (10 ml). The solution was stirred at rt overnight. Water was added and the mixture was extracted with EtOAc. The organic phase was rotovaped to produce 140 mg of Compound 25a. LC-MS (m/z) 441.4 (MH+), tR=1.44 min (method A). Compound 25a was dissolved in THF and LiOH (1M) was added and the mixture was stirred 30 min. A solid precipitated and was isolated by filtration and dried in vac. Yield of Compound 25=110 mg (34%).

References: [1]Patent: US2013/12530,2013,A1 .Location in patent: Paragraph 0278-0279.

51
[ 23020-15-7 ]
[ 1417656-34-8 ]
[ 1417655-93-6 ]

Yield	Reaction Conditions	Operation in experiment
29%		General procedure: Triethylamine (0.384 mL, 2.75 mmol) was added to a mixture of trans-2-phenyl-1-cyclopropanecarboxylic acid IM46 (223 mg, 1.38 mmol) and O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (522 mg, 1.38 mmol) suspended in DMF (2 mL) in a small vial. The vial was vigorously agitated for 30 seconds and then left for 5 minutes. This mixture was added drop wise to (R)-2-Amino-2-(6-propoxy-pyridin-3-yl)-ethanol IM36 (270 mg, 1.4 mmol) dissolved in DMF (3 mL). After 1 h the mixture was poured into a mixture of EtOAc (40 mL) and brine (20 mL). The organic layer was dried over MgSO4 and evaporated to dryness. Flash chromatography (silica, 10-100% EtOAc in heptanes) gave the title compound as a white solid (0.134 g, 29%). LC-MS (m/z) 341.0 (MH+), tR=1.52 min (method A). 1H-NMR (600 MHz, DMSO) δ 8.53 (d, J=8.2 Hz, 1H), 8.04 (br s, 1H), 7.64-7.57 (m, 1H), 7.30-7.23 (m, 2H), 7.19-7.14 (m, 1H), 7.10 (d, J=7.3 Hz, 2H), 6.74 (d, J=8.5 Hz, 1H), 4.96-4.90 (m, 1H), 4.88-4.80 (m, 1H), 4.16 (t, J=6.7 Hz, 2H), 3.61-3.49 (m, 2H), 2.23-2.15 (m, 1H), 2.04-1.95 (m, 1H), 1.74-1.64 (m, 2H), 1.40-1.32 (m, 1H), 1.23-1.13 (m, 1H), 0.94 (t, J=7.4 Hz, 3H).

References: [1]Patent: US2013/12530,2013,A1 .Location in patent: Paragraph 0270-0271.

52
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[ 1417656-32-6 ]
[ 1417655-73-2 ]

Yield	Reaction Conditions	Operation in experiment
67%		General procedure: Trans-2-phenyl-1-cyclopropanecarboxylic acid IM46 (0.590 g, 3.64 mmol) was dissolved in DMF (15.0 mL). N,N,N',N'-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (1.38 g, 3.63 mmol) was added. Triethylamine (1.10 mL, 7.89 mmol) was then added and the mixture was stirred for 15 minutes at room temperature. This mixture was added drop wise to a solution of (S)-146-isopropoxy-pyridin-3-yl)-ethylamine IM24 (0.655 g, 3.63 mmol) dissolved in DMF (15.0 mL) over 2 minutes. The mixture was stirred at room temperature over night. The mixture was evaporated to dryness. The residue was transferred to a silica gel column and eluded with EtOAc/heptanes 1:1 to give Compound 1 as a solid. This solid was dissolved in EtOAc (50 mL) and to this solution was slowly added heptanes (50 mL). The mixture was concentrated to approx. 25 mL in vacuo and this solution was cooled in an ice/water bath. A white precipitate formed. The solids was collected by filtration and dried in vacuo to give the title compound as colorless crystals (0.794 g, 67%). LC-MS (m/z) 325.4 (MH+), tR=1.51 min (method A). 1H NMR (500 MHz, DMSO) δ 8.57-8.50 (m, 1H), 8.06 (br s, 1H), 7.65-7.57 (m, 1H), 7.30-7.24 (m, 2H), 7.20-7.14 (m, 1H), 7.10 (d, J=7.5 Hz, 2H), 6.69 (d, J=8.5 Hz, 1H), 5.25-5.16 (m, 1H), 4.98-4.88 (m, 1H), 2.24-2.15 (m, 1H), 1.94-1.88 (m, 1H), 1.41-1.32 (m, 4H), 1.26 (d, J=6.2 Hz, 6H), 1.20 (ddd, J=8.5, 6.1, 4.1 Hz, 1H). Diastereomeric excess >95% based on 1H NMR.

References: [1]Patent: US2013/12530,2013,A1 .Location in patent: Paragraph 0230-0231.

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[ 23020-15-7 ]

References: [1]Organic Letters,2013,vol. 15,p. 1350 - 1353.

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[ 110659-58-0 ]
[ 23020-15-7 ]

References: [1]Organic Letters,2013,vol. 15,p. 1350 - 1353.

Historical Records

Technical Information

• Arndt-Eistert Homologation • Benzylic Oxidation • Birch Reduction • Blanc Chloromethylation • Friedel-Crafts Reaction • Halogenation • Heat of Combustion • Hunsdiecker-Borodin Reaction • Hydrogenolysis of Benzyl Ether • Passerini Reaction • Preparation of Alkylbenzene • Preparation of Amines • Preparation of Carboxylic Acids • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Reactions of Carboxylic Acids • Schmidt Reaction • Specialized Acylation Reagents-Ketenes • Ugi Reaction • Vilsmeier-Haack Reaction

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[ 23020-15-7 ]

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CAS No.: 23020-15-7

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