Boron trifluoride → (2S,3R,4R,5S,6R)-2-[3-[(4-benzylspiro[3H-1,4-benzoxazine-2,1'-cyclopropane]-6-yl)methyl]-4-chloro-phenyl]-6-(hydroxymethyl)tetrahydropyran-3,4,5-triol

HRID 72595Notes

Reaction equation

HRID 72595 reaction equation
[CH2:1]([N:8]1[C:15]2[CH:16]=[C:17]([CH2:20][C:21]3[CH:22]=[C:23]([C:28]4(OC)[C@H:33]([OH:34])[C@@H:32]([OH:35])[C@H:31]([OH:36])[C@@H:30]([CH2:37][OH:38])[O:29]4)[CH:24]=[CH:25][C:26]=3[Cl:27])[CH:18]=[CH:19][C:14]=2[O:13][C:10]2([CH2:12][CH2:11]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([SiH](CC)CC)C.B(F)(F)F>C(#N)C.ClCCl>[CH2:1]([N:8]1[C:15]2[CH:16]=[C:17]([CH2:20][C:21]3[CH:22]=[C:23]([C@H:28]4[C@H:33]([OH:34])[C@@H:32]([OH:35])[C@H:31]([OH:36])[C@@H:30]([CH2:37][OH:38])[O:29]4)[CH:24]=[CH:25][C:26]=3[Cl:27])[CH:18]=[CH:19][C:14]=2[O:13][C:10]2([CH2:12][CH2:11]2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6356Boron trifluorideHCID 12052TriethylsilaneHCID 58340874(3R,4S,5S,6R)-2-[3-[(4-benzylspiro[3H-1,4-benzoxazine-2,1'-cyclopropane]-6-yl)methyl]-4-chloro-phenyl]-6-(hydroxymethyl)-2-methoxy-tetrahydropyran-3,4,5-triol

Product 1

HCID 52913167(2S,3R,4R,5S,6R)-2-[3-[(4-benzylspiro[3H-1,4-benzoxazine-2,1'-cyclopropane]-6-yl)methyl]-4-chloro-phenyl]-6-(hydroxymethyl)tetrahydropyran-3,4,5-triolYield 92.9%

Reagents, catalysts & solvents 1

HCID 21877088Acetonitrile methylene chlorideSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of (3R,4S,5S,6R)-2-[3-[(4-benzylspiro[3H-1,4-benzoxazine-2,1′-cyclopropane]-6-yl)methyl]-4-chloro-phenyl]-6-(hydroxymethyl)-2-methoxy-tetrahydropyran-3,4,5-triol (340 mg, 0.6 mmol) in acetonitrile-dichloromethane (6 mL, 1:1 mixture) was added triethylsilane (0.4 mL, 2.4 mmol) and boron trifluoride diethyletharate complex (0.15 mL, 1.2 mmol) at −5° C. After stirring for 4 h at 0° C., the reaction was quenched with saturated aq. sodium bicarbonate solution (5 mL). The volatiles were evaporated under reduced pressure, and the resulting mixture was extracted with ethyl acetate (3×10 mL). The ethyl acetate layers were combined and washed with brine (10 mL), dried over sodium sulphate, and concentrated. The resulting residue was purified by silica gel column chromatography to furnish (2S,3R,4R,5S,6R)-2-[3-[(4-benzylspiro[3H-1,4-benzoxazine-2,1′-cyclopropane]-6-yl)methyl]-4-chloro-phenyl]-6-(hydroxymethyl)tetrahydropyran-3,4,5-triol (300 mg).

Workup

  1. customthe reaction was quenched with saturated aq. sodium bicarbonate solution (5 mL)
  2. customThe volatiles were evaporated under reduced pressure
  3. extractionthe resulting mixture was extracted with ethyl acetate (3×10 mL)
  4. washwashed with brine (10 mL)
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated
  7. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-d22a6c1885774caabdeffe9d44fd2d29
Source dataset
uspto-grants-2014_09
Patent number
US08828951B2

Reaction notes

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