2-amino-4-bromo-5-fluorobenzoic acid

 

2-amino-4-bromo-5-fluorobenzoic acid as a white to off-white crystalline solid

1H NMR (400 MHz, DMSO-d6) δ 7.62 (d, J=9.6 Hz, 1H), 7.21-6.5 (m, 3H), 3.8- 3.3 (br s, 1H).

13C NMR (100 MHz, DMSO-d6) δ 170.5, 149.6, 147.6, 147.3, 120.4, 118.1, 118.0, 109.2, 109.0, 99.5.

mp >250 °C. IR (neat) 3494, 3351, 3053, 3038, 1521, 774 cm-1;

HRMS (ESI) m/z: calcd for C7H5BrFNO2 [M+H]+ 233.9560, found 233.9551.

Org. Lett., 2018, 20 (13), pp 3736–3740

DOI: 10.1021/acs.orglett.8b01218

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Quetiapine

Quetiapine

1H NMR (400 MHz, CD3OD): δ = 3.18-3.27 (m, 4H), 3.35-3.44 (m, 3H), 3.56-3.58 (m, 3H), 3.67-3.69 (m, 3H), 3.76 (t, J = 5.2 Hz, 2H), 4.32 (s, 1H), 6.88 (td, J = 7.4 Hz, 1.2 Hz, 1H), 7.04 (dd, J = 7.8 Hz, 1.6 Hz, 1H), 7.13 (td, J = 7.8 Hz, 1.6 Hz, 1H), 7.23 (dd, J = 6.8 Hz, 2.4 Hz, 1H), 7.28-7.39 (m, 4H) ppm.

13C NMR (100 MHz, CD3OD): δ = 40.2, 45.6, 52.8, 53.3, 57.6, 62.0, 65.6, 73.4, 123.9, 125.99, 126.0, 128.4, 129.0, 130.6, 131.3, 132.5, 133.2, 134.7, 137.9, 145.7, 170.6 ppm.

HRMS (ESI+ ): calcd for C21H26N3O2S [M+H]+ 384.1740, found 384.1735.

Org. Lett., Article ASAP

DOI: 10.1021/acs.orglett.8b02812

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3-fluoro-4- morpholinoaniline

 

3-fluoro-4- morpholinoaniline

1H NMR (400MHz, CDCl3)  6.82 (m, 1H, ArH), 6.43 (m, 2H, 2xArH), 3.87 (m, 4H, 2xCH2O), 3.58 (brs, 2H, NH2), 2.99 (m, 4H, 2xCH2N). 13C NMR (100MHz, CDCl3)  156.9 (d J= 245.4Hz), 143.0 (d J=10.4Hz), 131.8 (d J=9.7Hz), 120.4 (d J=4.2Hz), 110.8 (d J=3.0Hz), 104.0 (d J=23.8Hz), 67.3, 51.9 (d J=2.1Hz). HRMS [M] Calcd for C10H13FN2O 196.1006, Found 196.1004.

 

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.8b00153

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4-(2-fluoro-4-nitrophenyl)morpholine

 

4-(2-fluoro-4-nitrophenyl)morpholine

1H NMR (400MHz, CDCl3)  8.03 (ddd J=1.0, 2.6 and 9.0Hz, 1H, ArH), 7.94 (dd J=2.6 and 13.1Hz, 1H, ArH), 6.94 (t J=8.7Hz, 1H, ArH), 3.90 (t J=4.7Hz, 4H, 2xCH2O), 3.31 (m, 4H, 2xCH2N).

13C NMR (100MHz, CDCl3)  153.3 (d J=249.5), 145.6 (d J=7.8Hz), 121.1 (d J=3.0Hz), 117.0 (d J=3.9Hz), 112.7 (d J=6.4Hz), 66.7, 50.0 (d J=4.9Hz).

HRMS [M] Calcd for C10H11FN2O3 226.0748, Found 226.0749.

Catalytic Static Mixers for the Continuous Flow Hydrogenation of a Key Intermediate of Linezolid (Zyvox)

James Gardiner, Xuan Nguyen, Charlotte Genet, Mike D. Horne, Christian H. Hornung, and John Tsanaktsidis

 

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.8b00153

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1-(4-Cyanophenyl)piperazine

1-(4-Cyanophenyl)piperazine

1-(4-Cyanophenyl)piperazine (1a).1 Isolated as a mixture of mono (1a) and di (3) arylated products ~9:1. Conversion: quantitative. Peaks attributed to 1a: 1H NMR (400 MHz, CD3Cl) δH 7.47 (m, 2H, arH), 6.83 (m, 2H, ar-H), 3.26 (m, 4H, pip-H), 2.99 (m, 4H, pip-H), 1.69 (br s, 1H, NH). Peaks attributed to 3: 7.52 (d, J = 9.0 Hz, 4H, ar-H), 6.88 (d, J = 9.0 Hz, 4H, ar-H), 3.29 (s, 8H, pip-H).

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.8b00090

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https://pubs.acs.org/doi/suppl/10.1021/acs.oprd.8b00090/suppl_file/op8b00090_si_001.pdf

Copper-catalyzed pyrrole synthesis from 3,6-dihydro-1,2-oxazines

Copper-catalyzed pyrrole synthesis from 3,6-dihydro-1,2-oxazines

 

Naoki Yasukawa,^a  Marina Kuwata,^a  Takuya Imai,^a  Yasunari Monguchi,^a  Hironao Sajiki*^a  and Yoshinari Sawama*^a 

 Author affiliations

*Corresponding authors

^aLaboratory of Organic Chemistry, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan
E-mail: sajiki@gifu-pu.ac.jp, sawama@gifu-pu.ac.jp
Fax: +81-58-230-8109

Abstract

Highly-functionalized pyrroles could be effectively synthesized from 3,6-dihydro-1,2-oxazines using a heterogeneous copper on carbon (Cu/C) under neat heating conditions. Furthermore, the in situ formation of 3,6-dihydro-1,2-oxazines via the hetero Diels–Alder reaction between nitroso dienophiles and 1,3-dienes and the following Cu/C-catalyzed pyrrole synthesis also provided the corresponding pyrrole derivatives in a one-pot manner.

Brown solid; M. p. 107–108 o C;
IR (ATR) cm-1 : 3064, 2923, 2851, 1687, 1596, 1562, 1541, 1498, 1488, 1459, 1451, 1422, 1390, 1343, 1319, 1256, 1187, 1098, 1073, 1053, 1037, 1009;
1 H NMR (500 MHz, CDCl3): δ 7.37–7.28 (m, 5H), 7.17 (d, J = 8.0 Hz, 2H), 6.99 (d, J = 8.0 Hz, 2H), 6.95 (dd, J = 2.0, 3.0 Hz, 1H), 6.45 (dd, J = 2.0, 3.0 Hz, 1H), 6.37 (dd, J = 3.0, 3.0 Hz, 1H);
13C NMR (125 MHz, CDCl3): δ 140.19, 132.52, 131.85, 131.19, 129.65, 129.14, 126.84, 125.69, 124.83, 120.24, 110.97, 109.38;
ESI-HRMS m/z: 298.0231([M+H+ ]); Calcd for C16H13NBr: 298.0226.
 

//////////3,6-dihydro-1,2-oxazines

TAFENOQUINE, タフェノキン

1 H NMR (300 MHz, CDCl3, TMS) d (ppm): 7.32 (q, 1H, J ¼ 18 Hz), 7.21 (d, 1H, J ¼ 6 Hz), 7.07 (s, 1H), 6.94 (d, 1H, J ¼ 6 Hz), 6.64 (s, 1H), 6.50 (s, 1H), 5.84 (d, 1H, J ¼ 6 Hz), 4.00 (s, 3H), 3.79 (s, 3H), 3.66 (s, 1H), 2.78 (d, 2H, J ¼ 6 Hz), 2.55 (s, 3H), 1.69 (dd, 6H, J ¼ 6 Hz, J ¼ 9 Hz), 1.35 (d, 3H, J ¼ 6 Hz). 

13C NMR (100 MHz, CDCl3, TMS) d (ppm): 159.64, 148.961, 146.339, 142.010, 132.085, 131.760, 131.007, 129.968, 126.917, 125.344, 122.636, 120.681, 118.006, 115.256, 112.052, 94.996, 56.989, 52.870, 48.446, 42.248, 34.439, 30.130, 23.103, 20.833. 

MS (m/z): M+ calcd for C24H28F3N3O3: 463.2083; found (ESI): 464.17 (M + H)+ .

PAPER

http://pubs.rsc.org/en/Content/ArticleLanding/2017/RA/C7RA04867J#!divAbstract

1H NMR PREDICT

13C NMR PREDICT

Synthesis   https://newdrugapprovals.org/2018/07/25/tafenoquine-%E3%82%BF%E3%83%95%E3%82%A7%E3%83%8E%E3%82%AD%E3%83%B3/