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

HRID 527974노트

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HRID 527974 반응식
[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

참가 물질

10

반응물 7

HCID 10311-Propanol2회HCID 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

생성물 1

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

시약·촉매·용매 2

HCID 22595341Propanol water용매HCID 53393272Potassium osmate(VI) dihydrate용매

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온도
10 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-31fed36ccfc842efab88188c72e565eb
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346804B2

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