1-Propanol → [1-(Fluoro-3-morpholin-4-yl-phenyl)-2-hydroxy-ethyl]-carbamic acid tert-butyl ester

HRID 857023Notes

Reaction equation

HRID 857023 reaction equation
[OH-].[Na+].[C:3](=[O:10])([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])[NH2:4].ClOC(C)(C)C.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(OC)C=C4)N(CC2)C1.[F:75][C:76]1C=[CH:80][C:79](C=C)=[CH:78][C:77]=1[N:84]1[CH2:89][CH2:88][O:87][CH2:86][CH2:85]1.[CH2:90]([OH:93])[CH2:91][CH3:92]>O.O.O.[Os](=O)(=O)=O.[K]>[C:6]([O:5][C:3](=[O:10])[NH:4][CH:91]([C:92]1[CH:80]=[CH:79][CH:78]=[C:77]([N:84]2[CH2:89][CH2:88][O:87][CH2:86][CH2:85]2)[C:76]=1[F:75])[CH2:90][OH:93])([CH3:9])([CH3:8])[CH3:7]

Participants

9

Reactant 6

HCID 10311-Propanol3×HCID 14798Sodium Hydroxide2×HCID 77922tert-Butyl carbamateHCID 521297Tert-Butyl hypochloriteHCID 112172021,4-Bis(dihydroquinidine)phthalazineHCID 218646624-(2-Fluoro-5-vinyl-phenyl)-morpholine

Product 1

HCID 69593465[1-(Fluoro-3-morpholin-4-yl-phenyl)-2-hydroxy-ethyl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 178526964HCID 178526964, compoundCatalyst2×HCID 962WaterSolvent

Procedure

Sodium hydroxide (3.6 g) was dissolved in water (220 mL). 10 mL of this solution was used to dissolve potassium osmium (VI) oxide dihydrate (434 mg) to get a purple suspension. The rest of the sodium hydroxide solution was treated with t-butyl carbamate (10.666 g) in n-propanol (120 mL), followed by addition of t-butyl hypochlorite (11 mL). This solution was stirred for 5 min, then (DHQD)2PHAL (1466 mg) in n-propanol (120 mL) was added, followed by a solution of 4-(2-Fluoro-5-vinyl-phenyl)-morpholine (5 g) in n-propanol (206 mL) and a solution of potassium osmium (VI) oxide dihydrate previously made. The reaction mixture was stirred at room temperature for 0.5 h. The reaction mixture was quenched with saturated Na2SO3 solution. After concentration, the residue was extracted with ethyl acetate. The combined organic layers were dried over magnesium sulfate, concentrated under vacuum. The crude product was purified by flash chromatography eluting with 33% ethyl acetate in hexanes to give the title compound as a solid (2.2 g).

Workup

  1. customto get a purple suspension
  2. stirringThe reaction mixture was stirred at room temperature for 0.5 h
  3. customThe reaction mixture was quenched with saturated Na2SO3 solution
  4. concentrationAfter concentration
  5. extractionthe residue was extracted with ethyl acetate
  6. dry with materialThe combined organic layers were dried over magnesium sulfate
  7. concentrationconcentrated under vacuum
  8. customThe crude product was purified by flash chromatography
  9. washeluting with 33% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-d410b3977e78406ba1664bdaccd42254
Source dataset
uspto-grants-2006_12
Patent number
US07144881B2

Reaction notes

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