Naphthalene → (S)-[2-amino-3-(1-fluoro-cyclohexyl)-propyl]-methyl-carbamic acid tert-butyl ester

HRID 1254360Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1254360
[Na:1].C1C2C(=CC=CC=2)C=CC=1.[F:12][C:13]1([CH2:19][CH:20]([NH:31]S(C2C=CC(C)=CC=2)(=O)=O)[CH2:21][N:22]([CH3:30])[C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1.[C-]1C2C(=CC=CC=2)C=CC=1.[Na+].CC1C=CC(S(N)(=O)=O)=CC=1>COCCOC.C(=O)=O.C(O)(C)C>[Na:1].[C:25]([O:24][C:23](=[O:29])[N:22]([CH2:21][C@@H:20]([NH2:31])[CH2:19][C:13]1([F:12])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]1)[CH3:30])([CH3:28])([CH3:26])[CH3:27]

Komponenten

9

Edukt 5

HCID 931NaphthaleneHCID 6269P-ToluenesulfonamideHCID 5360545SodiumHCID 13651362Sodium naphthalideHCID 59382997Tert-butyl 3-(1-fluorocyclohexyl)-2-(4-methylphenylsulfonamido)propyl(methyl)carbamate

Produkt 2

HCID 5360545SodiumHCID 67189377(S)-[2-amino-3-(1-fluoro-cyclohexyl)-propyl]-methyl-carbamic acid tert-butyl esterAusbeute 45 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 80711,2-DimethoxyethaneLösungsmittel3×HCID 86586944Isopropanol carbon dioxideLösungsmittel

Versuchsvorschrift

A solution of sodium naphalenide in anhydrous DME was prepared by adding anhydrous DME (20 mL) to a mixture of sodium (0.3 g, 13 mmol) and naphthalene (2.1 g, 16 mmol) and stirring the resulting mixture at rt for 2 h. A solution of tert-butyl 3-(1-fluorocyclohexyl)-2-(4-methylphenylsulfonamido)propyl(methyl)carbamate (200 mg, 0.43 mmol) in anhydrous DME (15 mL) was cooled in dry ice-isopropyl alcohol bath. The sodium naphthalenide solution was added dropwise to the well-stirred tosylamide solution until a light green color persisted. The reaction was quenched with water, diluted with EtOAc and washed with 1 N aq HCl. The aqueous phase was basified with K2CO3, and extracted with EtOAc (3×20 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo to give (S)-[2-amino-3-(1-fluoro-cyclohexyl)-propyl]-methyl-carbamic acid tert-butyl ester (50 mg, 45%).

Aufarbeitung

  1. customThe reaction was quenched with water
  2. additiondiluted with EtOAc
  3. washwashed with 1 N aq HCl
  4. extractionextracted with EtOAc (3×20 mL)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-5bfe9c2a924346198af97fbbb50c3e4c
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08455521B2

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