Technology Process of (S)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydrospiro[benzo[d][1,3]oxazine-4,4'-piperidine]-1'-yl)-2-methylbutanoic acid
There total 9 articles about (S)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydrospiro[benzo[d][1,3]oxazine-4,4'-piperidine]-1'-yl)-2-methylbutanoic acid which
guide to synthetic route it.
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synthetic route:
- Guidance literature:
-
6-fluoro-1-methylspiro[benzo[d][1,3]oxazine-4,4'-piperidin]-2(1H)-one; (S)-3-(3,4-dichlorophenyl)-5-hydroxy-3-methyldihydrofuran-2(3H)-one;
In
1,2-dichloro-ethane;
at 20 ℃;
for 18h;
Molecular sieve;
Inert atmosphere;
With
sodium tris(acetoxy)borohydride;
In
1,2-dichloro-ethane;
at 20 ℃;
for 24h;
Inert atmosphere;
DOI:10.1021/ml400528y
- Guidance literature:
-
Multi-step reaction with 4 steps
1.1: tert.-butyl lithium / tetrahydrofuran; pentane / 4.5 h / -78 - -15 °C / Inert atmosphere
1.2: 0.42 h / -78 °C / Inert atmosphere
1.3: 13 h / -78 - 70 °C / Inert atmosphere
2.1: caesium carbonate / N,N-dimethyl-formamide / 16 h / 20 °C / Inert atmosphere; Molecular sieve
3.1: trifluoroacetic acid / dichloromethane / 16 h / 0 - 20 °C / Inert atmosphere
4.1: 1,2-dichloro-ethane / 18 h / 20 °C / Molecular sieve; Inert atmosphere
4.2: 24 h / 20 °C / Inert atmosphere
With
tert.-butyl lithium; caesium carbonate; trifluoroacetic acid;
In
tetrahydrofuran; dichloromethane; 1,2-dichloro-ethane; N,N-dimethyl-formamide; pentane;
DOI:10.1021/ml400528y
- Guidance literature:
-
Multi-step reaction with 8 steps
1.1: lithium hexamethyldisilazane / tetrahydrofuran; pentane / 2 h / -25 °C / Inert atmosphere
1.2: 1.27 h / -25 - 20 °C / Inert atmosphere
2.1: thionyl chloride / 11.33 h / 20 °C / Inert atmosphere; Cooling with ice
3.1: sodium hydride / tetrahydrofuran; N,N-dimethyl-formamide; mineral oil / 5 h / 0 - 20 °C / Inert atmosphere
3.2: 2 h / 20 °C / Inert atmosphere
4.1: lithium hydroxide; water / methanol / 10 h / Reflux
5.1: ethyl acetate / Resolution of racemate; Inert atmosphere
6.1: hydrogenchloride / ethyl acetate; water
7.1: osmium(VIII) oxide; sodium periodate / tetrahydrofuran; water / 18 h / 20 °C / Darkness
8.1: 1,2-dichloro-ethane / 18 h / 20 °C / Molecular sieve; Inert atmosphere
8.2: 24 h / 20 °C / Inert atmosphere
With
hydrogenchloride; sodium periodate; osmium(VIII) oxide; thionyl chloride; water; sodium hydride; lithium hydroxide; lithium hexamethyldisilazane;
In
tetrahydrofuran; methanol; water; ethyl acetate; 1,2-dichloro-ethane; N,N-dimethyl-formamide; mineral oil; pentane;
DOI:10.1021/ml400528y