Sodium Methoxide → Ertugliflozin Impurity 10

HRID 59202Notes

Reaction equation

HRID 59202 reaction equation
C([O:4][C@@H:5]1[C@@H:11]([O:12]C(=O)C)[C@:10]2([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([C:24](=[O:34])[C:25]4[CH:30]=[CH:29][C:28]([O:31][CH2:32][CH3:33])=[CH:27][CH:26]=4)[CH:18]=3)[O:16][C@@:7]([CH2:35][O:36]C(=O)C)([CH2:8][O:9]2)[C@H:6]1[O:40]C(=O)C)(=O)C.C[O-].[Na+]>CO.O1CCCC1>[Cl:23][C:20]1[CH:21]=[CH:22][C:17]([C@@:10]23[O:16][C@@:7]([CH2:35][OH:36])([CH2:8][O:9]2)[C@@H:6]([OH:40])[C@H:5]([OH:4])[C@H:11]3[OH:12])=[CH:18][C:19]=1[C:24]([C:25]1[CH:26]=[CH:27][C:28]([O:31][CH2:32][CH3:33])=[CH:29][CH:30]=1)=[O:34]

Participants

5

Reactant 2

HCID 10942334Sodium MethoxideHCID 67153925HCID 67153925, compound

Product 1

HCID 52931639Ertugliflozin Impurity 10Yield 98.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of acetic acid (1R,2S,3S,4R,5S)-3,4-diacetoxy-1-acetoxymethyl-5-[4-chloro-3-(4-ethoxy-benzoyl)-phenyl]-6,8-dioxa-bicyclo[3.2.1]oct-2-yl ester (see Example 11 for preparation; 65 mg, 0.10 mmol) in methanol (3 mL) and tetrahydrofuran (2 mL) was added sodium methoxide in methanol (25% wt) until pH 12 was obtained and the resulting mixture was stirred at room temperature. After 16 hours, the reaction mixture was neutralized by the addition of Dowex Monosphere 650C (H) cation exchange resin until the pH of the solution was <7, filtered and concentrated under reduced pressure. The resulting material was precipitated from ethyl acetate and heptanes and the resulting white solid was washed with heptane 2 times and dried under reduced pressure to yield the desired product (44.5 mg, 94% yield). MS (LCMS) 451.1 (M+H+; positive mode)1H NMR (400 MHz, METHANOL-d4) delta ppm 1.40 (t, J=6.9 Hz, 3 H), 3.55 (d, J=8.0 Hz, 1 H), 3.60 (d, J=7.4 Hz, 1 H), 3.65 (t, J=8.1 Hz, 1 H), 3.67 (d, J=12.5 Hz, 1 H), 3.77 (d, J=8.0 Hz, 1 H), 3.83 (d, J=12.5 Hz, 1 H), 4.12 (q, J=7.0 Hz, 2 H), 4.14 (d, J=7.6 Hz, 1 H), 6.98 (d, J=8.8 Hz, 2 H), 7.48 (d, J=8.4 Hz, 1 H), 7.52 (d, J=2.0 Hz, 1 H), 7.65 (dd, J=8.4, 2.0 Hz, 1 H), 7.73 (d, J=8.8 Hz, 2 H). HRMS calculated for C22H23O8Cl (M) 450.1081. found 450.1079.

Workup

  1. customwas obtained
  2. filtrationfiltered
  3. concentrationconcentrated under reduced pressure
  4. customThe resulting material was precipitated from ethyl acetate and heptanes
  5. washthe resulting white solid was washed with heptane 2 times
  6. customdried under reduced pressure

Sources & evidence

ORD record
ord-5d496bbe36914835981cf97306bd7578
Source dataset
uspto-grants-2016_09
Patent number
US09439901B2

Reaction notes

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