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

HRID 454979Notes

Reaction equation

HRID 454979 reaction equation
C(O[NH:6][C:7](=O)[O-:8])(C)(C)C.[OH-:10].[Na+].[C:12]([O:16]Cl)([CH3:15])([CH3:14])[CH3:13].CC[C@@H]1[C@@H]2C[C@H]([C@@H](OC3[C:51]4[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=4)[C:45]([O:52][C@@H:53]([C:64]4C=CN=[C:70]5[C:65]=4[CH:66]=C(OC)[CH:68]=[CH:69]5)[C@@H:54]4N5C[C@H](CC)[C@@H](CC5)[CH2:55]4)=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:12]([O:16][C:7](=[O:8])[NH:6][C@H:69]([C:70]1[CH:55]=[CH:54][C:53]([O:52][CH2:45][C:46]2[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=2)=[CH:64][C:65]=1[CH3:66])[CH2:68][OH:10])([CH3:15])([CH3:14])[CH3:13]

Participants

8

Reactant 5

HCID 7501StyreneHCID 14798Sodium HydroxideHCID 521297Tert-Butyl hypochloriteHCID 112172021,4-Bis(dihydroquinidine)phthalazineHCID 21873768Tert-butoxycarbamate

Product 1

HCID 67074428[(R)-1-(4-Benzyloxy-2-methyl-phenyl)-2-hydroxy-ethyl]-carbamic acid tert-butyl esterYield 918.1%

Reagents, catalysts & solvents 2

HCID 10311-PropanolSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

To 15.36 g (131.1 mmol) of tert-butoxycarbamate suspended in 100 mL propanol was added 150 mL 0.87 M NaOH (131.1 mmol), and freshly prepared tBuOCl (14.9 g 131.1 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 (2.0 g, 2.59 mmol) dissolved in 30 mL PrOH. This was followed by the addition of the styrene (9.64 g, 42.99 mmol) also dissolved in 20 mL PrOH, and stirred for another 8 min. Then K2OsO4.2H2O 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 8.5 g (55%) of the product.

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-559aef8605b14a68acd080e696da623a
Source dataset
uspto-grants-2013_07
Patent number
US08497271B2

Reaction notes

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