tert-Butanol → HCID 59989618, compound

HRID 982658Notes

Reaction equation

HRID 982658 reaction equation
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([O:22]C)C=C4)N(CC2)C1.CS(N)(=O)=O.[CH2:64]([O:71][C:72](=[O:82])[C@H:73]([N:75]1[C:80](=[O:81])C=CC[O:76]1)[CH3:74])[C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1.S([O-])([O-])=O.[Na+].[Na+].[C:89]([OH:93])([CH3:92])(C)[CH3:90]>O.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>[CH2:64]([O:71][C:72]([C@H:73]([N:75]1[C:80](=[O:81])[C@@H:90]([OH:22])[C@@H:89]([OH:93])[CH2:92][O:76]1)[CH3:74])=[O:82])[C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1

Participants

8

Reactant 5

HCID 6386tert-ButanolHCID 24437Sodium SulfiteHCID 72879MethanesulfonamideHCID 11196278HCID 11196278, compoundHCID 112172021,4-Bis(dihydroquinidine)phthalazine

Product 1

HCID 59989618HCID 59989618, compoundYield 81%

Reagents, catalysts & solvents 2

HCID 112172021,4-Bis(dihydroquinidine)phthalazineCatalystHCID 962WaterSolvent

Procedure

A mixture of K2OsO2(OH)4 (0.0063 g, 0.017 mmol), (DHQD)2PHAL (0.032 g, 0.041 mmol), and AD-mix-β (1.41 g) was dissolved in a mixture of tert-butanol (5 mL) and water (5 mL). After dissolution of the salts, methanesulfonamide (0.0994 g, 1.04 mmol) was added and the mixture was cooled to −2˜0° C. (R)-2-(α-Benzoxycarbonylethyl)-4,5-dehydro-1,2-oxazinan-3-one (7a) (0.264 g, 1.01 mmol) was added in one portion and the heterogeneous slurry was stirred vigorously for 14 h at −2˜+2° C. Sodium sulfite (1.5 g) was added in order to quench the oxidation and stirring was continued for 1 h at RT. CH2Cl2 (10 mL) was added and the upper organic layer was separated off. The aqueous phase was extracted with CH2Cl2 (5×5 mL). The combined organic extracts were dried over MgSO4. After removal of the solvent, the yellowish semisolid residue was purified by dry flash chromatography (Silica Gel 60H for TLC, 15% EtOAc-hexanes→EtOAc) to afford 0.158 g (81%) the product 8a as a white solid. 1H NMR (400 MHz) in CDCl3+2 drops of CD3OD (J, Hz): δ 1.53 (3H, d, 3J=7.3, α-MeCH), 3.96 (1H, dd, 2J=−11.8, 3J=2.5, 6-HA), 4.41 (1H, d, 3J=4.1, 4-H), 4.44 (1H, dd, 2J=−11.8, 3J=6.8, 6-HB), 4.55-4.51 (1H, m, 5-H), 5.11 (1H, q, 3J=7.3, α-CH), 5.13 (1H, s, CH2Ph), 7.34-7.24 (5H, m, Ph).

Workup

  1. additionwas added
  2. additionwas added in one portion
  3. customto quench the oxidation
  4. stirringstirring
  5. waitwas continued for 1 h at RT
  6. additionCH2Cl2 (10 mL) was added
  7. customthe upper organic layer was separated off
  8. extractionThe aqueous phase was extracted with CH2Cl2 (5×5 mL)
  9. dry with materialThe combined organic extracts were dried over MgSO4
  10. customAfter removal of the solvent
  11. customthe yellowish semisolid residue was purified
  12. dry with materialby dry flash chromatography (Silica Gel 60H for TLC, 15% EtOAc-hexanes→EtOAc)

Sources & evidence

ORD record
ord-f3f5f2e816e5403cb901f27ad517b3f8
Source dataset
uspto-grants-2005_03
Patent number
US06861416B2

Reaction notes

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