1-Propanol → (2S*,3R*)-3-tert-butoxycarbonylamino-2-hydroxy-3-(2-methoxy-quinolin-8-yl)-propionic acid methyl ester

HRID 527974Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 527974
[C:1](=[O:8])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])[NH2:2].[OH-:9].[Na+].ClO[C:13]([CH3:16])([CH3:15])[CH3:14].CC[C@@H]1[C@@H]2C[C@H]([C@@H](OC3[C:50]4[C:45](=C[CH:47]=[CH:48][CH:49]=4)[C:44]([O:51][C@@H:52](C4C=CN=C5C=4C=C(OC)C=C5)[C@@H]4N5C[C@H](CC)[C@@H](CC5)C4)=[N:43]N=3)C3C=CN=C4C=3C=C(OC)C=C4)N(CC2)C1.CC[C@H]1[C@H]2C[C@H]([C@H](OC3C4C(=CC=CC=4)C(O[C@H](C4C=CN=C5C=4C=C(OC)C=C5)[C@@H]4N5C[C@H](CC)[C@@H](CC5)C4)=NN=3)C3C=CN=C4C=3C=[C:89]([O:96]C)C=C4)N(CC2)C1.[O-]S([O-])=O.[Na+].[Na+].[CH2:139]([OH:142])[CH2:140]C>O.C(O)CC.O.O.[O-][Os]([O-])(=O)=O.[K+].[K+]>[CH3:89][O:96][C:139](=[O:142])[C@@H:140]([OH:9])[C@H:14]([NH:2][C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:8])[C:13]1[CH:16]=[CH:47][CH:48]=[C:49]2[C:15]=1[N:43]=[C:44]([O:51][CH3:52])[CH:45]=[CH:50]2

Komponenten

10

Edukt 7

HCID 10311-Propanol2×HCID 14798Sodium HydroxideHCID 24437Sodium SulfiteHCID 77922tert-Butyl carbamateHCID 521297Tert-Butyl hypochloriteHCID 112172021,4-Bis(dihydroquinidine)phthalazineHCID 510036741-((1R)-((2R,4R,5S)-5-ethylquinuclidin-2-yl)(6-methoxyquinolin-4-yl)methoxy)-4-((1R)-((2R,4S,5R)-5-ethylquinuclidin-2-yl)(6-methoxyquinolin-4-yl)methoxy)phthalazine

Produkt 1

HCID 90149690(2S*,3R*)-3-tert-butoxycarbonylamino-2-hydroxy-3-(2-methoxy-quinolin-8-yl)-propionic acid methyl esterAusbeute 63 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 22595341Propanol waterLösungsmittelHCID 53393272Potassium osmate(VI) dihydrateLösungsmittel

Reaktionsbedingungen

Temperatur
10 °C

Versuchsvorschrift

A solution of tert-butyl carbamate (7.06 g) in n-propanol (120 mL) was sequentially treated with 0.4M NaOH (218 mL) and tert-butyl hypochlorite (10.6 mL; freshly prepared as described in Org. Lett. (2003), 5(12), 2123-2126 (S-2)). The reaction mixture was treated with a solution of (DHQD)2PHAL (565 mg) and (DHQ)2PHAL (565 mg) in n-propanol (100 mL) and after 5 min cooled to 10° C. and sequentially treated with a suspension of intermediate BQ.i. (7.07 g) in water/n-propanol (1:1; 140 mL) and potassium osmate(VI) dihydrate (428 mg). After stirring at +10° C. for 20 min the reaction mixture was treated with Na2SO3 (15 g) and further stirred at rt for 10 min. The reaction mixture was extracted with EA and the org. layer was sequentially washed with 5% aq. K2CO3, sat. aq. NaHCO3 and brine. After drying over MgSO4 and evaporation of the solvent, the residue was purified by CC (DCM/MeOH 10-1 containing 1% NH4OH), affording a pale yellow foam (6.85 g; 63% yield).

Aufarbeitung

  1. customfreshly prepared
  2. additionsequentially treated with a suspension of intermediate BQ.i
  3. stirringfurther stirred at rt for 10 min
  4. extractionThe reaction mixture was extracted with EA
  5. washlayer was sequentially washed with 5% aq. K2CO3, sat. aq. NaHCO3 and brine
  6. dry with materialAfter drying over MgSO4 and evaporation of the solvent
  7. customthe residue was purified by CC (DCM/MeOH 10-1 containing 1% NH4OH)
  8. customaffording a pale yellow foam (6.85 g; 63% yield)

Quellen und Nachweise

ORD-Eintrag
ord-31fed36ccfc842efab88188c72e565eb
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09346804B2

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