Styrene → [(R)-1-(4-benzyloxy-2-methoxy-phenyl)-2-hydroxy-ethyl]-carbamic acid tert-butyl ester

HRID 454967Notes

Reaction equation

HRID 454967 reaction equation
[C:1]([NH:5][C:6](=[O:8])[O-])(C)(C)[CH3:2].[OH-:9].[Na+].[C:11]([O:15]Cl)([CH3:14])([CH3:13])[CH3:12].CC[C@@H]1[C@@H]2C[C@H]([C@@H](OC3[C:50]4[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=4)[C:44]([O:51][C@@H:52]([C:63]4C=CN=C5[C:64]=4[CH:65]=[C:66]([O:73][CH3:74])[CH:67]=C5)[C@@H]4N5C[C@H](CC)[C@@H](CC5)C4)=NN=3)C3C=CN=C4C=3C=C(OC)C=C4)N(CC2)C1.C=CC1C=CC=CC=1>C(O)CC.CCOC(C)=O>[C:11]([O:15][C:6](=[O:8])[NH:5][C@H:1]([C:65]1[CH:64]=[CH:63][C:52]([O:51][CH2:44][C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)=[CH:67][C:66]=1[O:73][CH3:74])[CH2:2][OH:9])([CH3:14])([CH3:13])[CH3:12]

Participants

8

Reactant 5

HCID 7501StyreneHCID 14798Sodium HydroxideHCID 521297Tert-Butyl hypochloriteHCID 112172021,4-Bis(dihydroquinidine)phthalazineHCID 21252905Tert-butylcarbamate

Product 1

HCID 67073951[(R)-1-(4-benzyloxy-2-methoxy-phenyl)-2-hydroxy-ethyl]-carbamic acid tert-butyl esterYield 415.9%

Reagents, catalysts & solvents 2

HCID 10311-PropanolSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

To 569 mg (4.86 mmol) of t-butylcarbamate suspended in 6.3 ml n-propanol was added 4.8 ml 1 N NaOH (4.8 mmol), and freshly prepared tBuOCl (548 ul, 4.8 mmol) and then stirred for 8 min at rt. It was then cooled to 0° C. followed by the addition of the catalyst (DHQD)2PHAL (73.2 mg, 0.094 mmol) dissolved in 6.3 ml n-PrOH. This was followed by the addition of the styrene (307 mg, 1.28 mmol) also dissolved in 11 ml n-PrOH, and stirred for another 8 min. Then K2OsO4.2H2O (23 mg, 0.063 mmol) was added directly, and the resulting mixture stirred for 1.5 hr at 0° C. Several color changes were observed, from brown, to bright red, to orange and then finally light yellow. Dilute with EtOAc, and quench with aq. Na2S2O3. The organic layer was separated and the aqueous layer extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4, and concentrated. It was purified on the ISCO using 5-50% EtOAc/hex to obtain 146 mg (30%) of the titled compound.

Workup

  1. temperatureIt was then cooled to 0° C.
  2. stirringstirred for another 8 min
  3. stirringthe resulting mixture stirred for 1.5 hr at 0° C
  4. customquench with aq. Na2S2O3
  5. customThe organic layer was separated
  6. extractionthe aqueous layer extracted with EtOAc
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. customIt was purified on the ISCO

Sources & evidence

ORD record
ord-a352581dc0044dfd9ec118b17dc2c34d
Source dataset
uspto-grants-2013_07
Patent number
US08497271B2

Reaction notes

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