tert-Butanol → (R)-4-Hydroxy-4-hydroxymethyl-6-chloro-8-difluoromethoxychromane
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.C=C1C2[C:64](=[C:65]([O:71][CH:72]([F:74])[F:73])[CH:66]=[C:67]([Cl:70])[CH:68]=2)[O:63][CH2:62]C1.S([O-])([O-])=O.[Na+].[Na+].[C:81]([OH:85])([CH3:84])([CH3:83])[CH3:82]>O>[OH:85][C@@:81]1([CH2:84][OH:22])[C:83]2[C:64](=[C:65]([O:71][CH:72]([F:74])[F:73])[CH:66]=[C:67]([Cl:70])[CH:68]=2)[O:63][CH2:62][CH2:82]1Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
To a mixture of tert-butanol (46 mL) and water (46 mL) was added AD-mix-β (18.6 g). The mixture was cooled to 0° C. 4-Methylene-6-chloro-8-difluoromethoxychromane (3.2 g 12.97 mmol, see step (vi) above) in tert-butanol (11 mL) and water (11 mL) was added. The mixture was stirred at 0° C. for 24 h. Sodium sulfite (19.0 g, 150.74 mmol) was added, and the mixture was allowed to warm to room temperature and stirred for 1 h. The layers were separated and the aqueous phase was extracted with EtOAc (2×). The combined ethyl acetate phases were dried (Na2SO4) and evaporated. The crude product was chromatographed on silica gel, eluting with methylene chloride:ethyl acetate (4:6), to afford 3.2 g (88%) of the sub-title compound.
Workup
- temperatureto warm to room temperature
- stirringstirred for 1 h
- customThe layers were separated
- extractionthe aqueous phase was extracted with EtOAc (2×)
- dry with materialThe combined ethyl acetate phases were dried (Na2SO4)
- customevaporated
- customThe crude product was chromatographed on silica gel
- washeluting with methylene chloride:ethyl acetate (4:6)
Sources & evidence
- ORD record
- ord-d7c10adf2d43404c9a0b684a9241d702
- Source dataset
- uspto-grants-2004_06
- Patent number
- US06750243B1
Reaction notes
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