Boron trifluoride etherate → Dapagliflozin

HRID 718218Notes

Reaction equation

HRID 718218 reaction equation
C([SiH](CC)CC)C.B(F)(F)F.CCOCC.[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([C@@:24]2(OC)[C@H:29]([OH:30])[C@@H:28]([OH:31])[C@H:27]([OH:32])[C@@H:26]([CH2:33][OH:34])[O:25]2)=[CH:20][C:19]=1[CH2:37][C:38]1[CH:43]=[CH:42][C:41]([O:44][CH2:45][CH3:46])=[CH:40][CH:39]=1>ClCCl.C(#N)C>[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([C@H:24]2[C@H:29]([OH:30])[C@@H:28]([OH:31])[C@H:27]([OH:32])[C@@H:26]([CH2:33][OH:34])[O:25]2)=[CH:20][C:19]=1[CH2:37][C:38]1[CH:39]=[CH:40][C:41]([O:44][CH2:45][CH3:46])=[CH:42][CH:43]=1

Participants

6

Reactant 3

HCID 8000Boron trifluoride etherate2×HCID 12052Triethylsilane2×HCID 24807437Methyl 1-C-{4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl}-alpha-D-glucopyranoside2×

Product 1

HCID 9887712Dapagliflozin

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent3×HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-22.5 °C

Procedure

To a 100 mL 3-neck flask equipped with magnetic stirrer and under argon atmosphere was added dichloromethane (7.0 mL), acetonitrile (7.0 mL) and triethylsilane (5.09 mL, 31.9 mmol) successively at room temperature. The above mixture was cooled to −20 to −25° C. and BF3.Et2O (3.03 mL, 23.9 mmol) was added in one portion. Another 100 mL flask was charged with crude (2S,3R,4S,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol (3.5 g, 7.97 mmol), dichloromethane (7.0 mL) and acetonitrile (7.0 mL), and the resulting mixture was shaking for 20 min at ambient temperature until a clear solution was obtained. Under an atmosphere of nitrogen, the (2S,3R,4S,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol solution in dichloromethane and acetonitrile was transferred to an addition funnel and was slowly added to the solution of BF3-Et2O and triethylsilane over a period of 1 h while keeping the internal temperature between −15 to −20° C. After the addition was completed, the mixture was stirred at a temperature between −15 to −20° C.

Workup

  1. customTo a 100 mL 3-neck flask equipped with magnetic stirrer and under argon atmosphere
  2. customwas obtained
  3. custombetween −15 to −20° C
  4. additionAfter the addition
  5. stirringthe mixture was stirred at a temperature between −15 to −20° C.

Sources & evidence

ORD record
ord-db92ed607785465e83ee0c2960067d77
Source dataset
uspto-grants-2015_11
Patent number
US09193751B2

Reaction notes

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