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

HRID 527974Notes

Reaction equation

HRID 527974 reaction equation
[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

Participants

10

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 22595341Propanol waterSolventHCID 53393272Potassium osmate(VI) dihydrateSolvent

Conditions

Temperature
10 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-31fed36ccfc842efab88188c72e565eb
Source dataset
uspto-grants-2016_05
Patent number
US09346804B2

Reaction notes

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