tert-Butyl Formate → {(3R,4S,5S)-5-[3-Fluoro-4-nitro-5-((R)-2,2,2-trifluoro-1-methoxymethyl-ethoxy)-benzyl]-4-hydroxy-tetrahydro-thiopyran-3-yl}-carbamic acid tert-butyl ester

HRID 420318

Reaktionsgleichung

Reaktionsgleichung von HRID 420318
[C:1]([O:5][C:6](=[O:27])[NH:7][C@@H:8]1[C@@H:13]([OH:14])[C@H:12]([CH2:15][C:16]2[CH:21]=[C:20]([F:22])[C:19]([N+:23]([O-:25])=[O:24])=[C:18](F)[CH:17]=2)[CH2:11][S:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[F:28][C:29]([F:36])([F:35])[C@H:30]([OH:34])[CH2:31][O:32][CH3:33].C(O[K])(C)(C)C.C(OC(C)(C)C)=O>C1COCC1.C1(C)C=CC=CC=1>[C:1]([O:5][C:6](=[O:27])[NH:7][C@@H:8]1[C@@H:13]([OH:14])[C@H:12]([CH2:15][C:16]2[CH:17]=[C:18]([O:34][C@H:30]([CH2:31][O:32][CH3:33])[C:29]([F:36])([F:35])[F:28])[C:19]([N+:23]([O-:25])=[O:24])=[C:20]([F:22])[CH:21]=2)[CH2:11][S:10][CH2:9]1)([CH3:3])([CH3:2])[CH3:4]

Komponenten

7

Edukt 4

HCID 61207tert-Butyl FormateHCID 57386308[(3R,4S,5S)-5-(3,5-difluoro-4-nitro-benzyl)-4-hydroxy-tetrahydro-thiopyran-3-yl]-carbamic acid tert-butyl esterHCID 866395431204343-96-3HCID 178418922HCID 178418922, Verbindung

Produkt 1

HCID 66649544{(3R,4S,5S)-5-[3-Fluoro-4-nitro-5-((R)-2,2,2-trifluoro-1-methoxymethyl-ethoxy)-benzyl]-4-hydroxy-tetrahydro-thiopyran-3-yl}-carbamic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140TolueneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of [(3R,4S,5S)-5-(3,5-difluoro-4-nitro-benzyl)-4-hydroxy-tetrahydro-thiopyran-3-yl]-carbamic acid tert-butyl ester (1 g, 2.47 mmol) and (R)-1,1,1-trifluoro-3-methoxy-propan-2-ol (392 mg, 2.72 mmol) in THF (13 mL) was added tert-BuOK (277 mg, 2.47 mmol) in small portions at 0° C. over a period of 30 min. After 1 h the cooling bath was removed and the orange solution was stirred at room temperature for 5 h. The reaction mixture was diluted with EtOAc (500 mL) and washed with ice cooled K2CO3 solution and cold brine. The organic phase was dried over Na2SO4, filtered and evaporated to yield a brown-yellowish foam: TLC Rf=0.50 (toluene-ETA 85:15); HPLC RtE=1.157 min; ESIMS [M+H-Boc]+=429; 1H NMR (600 MHz, DMSO-d6): δ 7.28 (s, 1H), 7.10 (d, 1H), 6.71 (d, 1H), 5.65 (broad, 1H), 4.95 (d, 1H), 3.83 (dd, 1H), 3.73 (dd, 1H), 3.42 (m, 1H), 3.31 (s, 3H), 3.25 (dd, 1H), 2.93 (m, 1H), 2.54 (d, 1H), 2.48-2.35 (m, 2H), 2.32-2.20 (m, 2H), 1.94 (m, 1H), 1.37 (s, 9H).

Aufarbeitung

  1. customAfter 1 h the cooling bath was removed
  2. additionThe reaction mixture was diluted with EtOAc (500 mL)
  3. washwashed with ice
  4. temperaturecooled K2CO3 solution and cold brine
  5. dry with materialThe organic phase was dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customto yield a brown-yellowish foam
  9. customHPLC RtE=1.157 min

Quellen und Nachweise

ORD-Eintrag
ord-2c76eaebf9314f3f950f4a41cdbeb8a5
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08093406B2

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