Hydrochloric Acid → (2S,3R,4R,5S,6R)-2-[4-chloro-3-(spiro[3,4-dihydro-1,4-benzoxazine-2,1'-cyclopropane]-6-ylmethyl)phenyl]-6-(hydroxymethyl)tetrahydropyran-3,4,5-triol

HRID 72596Notes

Reaction equation

HRID 72596 reaction equation
C([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)C1C=CC=CC=1.C(OCC)(=O)C.Cl>CO.[Pd]>[Cl:27][C:26]1[CH:25]=[CH:24][C:23]([C@H:28]2[C@H:33]([OH:34])[C@@H:32]([OH:35])[C@H:31]([OH:36])[C@@H:30]([CH2:37][OH:38])[O:29]2)=[CH:22][C:21]=1[CH2:20][C:17]1[CH:18]=[CH:19][C:14]2[O:13][C:10]3([CH2:12][CH2:11]3)[CH2:9][NH:8][C:15]=2[CH:16]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 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-triol

Product 1

HCID 52913168(2S,3R,4R,5S,6R)-2-[4-chloro-3-(spiro[3,4-dihydro-1,4-benzoxazine-2,1'-cyclopropane]-6-ylmethyl)phenyl]-6-(hydroxymethyl)tetrahydropyran-3,4,5-triolYield 22.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of (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) in methanol (3 mL), was added ethyl acetate (0.5 mL), 10% palladium on charcoal (40 mg), and 0.3 mL conc. HCl. The reaction mixture was stirred under hydrogen balloon pressure for 2 h then filtered through a celite bed which was washed with methanol, and the resulting filtrate was concentrated to a residue which was purified by preparative HPLC to furnish (2S,3R,4R,5S,6R)-2-[4-chloro-3-(spiro[3,4-dihydro-1,4-benzoxazine-2,1′-cyclopropane]-6-ylmethyl)phenyl]-6-(hydroxymethyl)tetrahydropyran-3,4,5-triol (56 mg).

Workup

  1. filtrationthen filtered through a celite bed which
  2. washwas washed with methanol
  3. concentrationthe resulting filtrate was concentrated to a residue which
  4. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-75ef6b609089414e99d4987272540cfe
Source dataset
uspto-grants-2014_09
Patent number
US08828951B2

Reaction notes

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