Hydrochloric Acid → Ipragliflozin

HRID 218986Notes

Reaction equation

CO.C([O:6][C@@H:7]1[C@@H:12]([O:13]C(=O)C)[C@H:11]([O:17]C(=O)C)[C@@H:10]([CH2:21][O:22]C(=O)C)[O:9][C@H:8]1[C:26]1[CH:31]=[CH:30][C:29]([F:32])=[C:28]([CH2:33][C:34]2[S:35][C:36]3[CH:42]=[CH:41][CH:40]=[CH:39][C:37]=3[CH:38]=2)[CH:27]=1)(=O)C.[OH-].[Na+].Cl>O>[S:35]1[C:36]2[CH:42]=[CH:41][CH:40]=[CH:39][C:37]=2[CH:38]=[C:34]1[CH2:33][C:28]1[CH:27]=[C:26]([C@@H:8]2[O:9][C@H:10]([CH2:21][OH:22])[C@@H:11]([OH:17])[C@H:12]([OH:13])[C@H:7]2[OH:6])[CH:31]=[CH:30][C:29]=1[F:32]

Participants

Conditions

Temperature: 44.54999923706055 °C

Procedure

To a methanol (427.4 kg) solution of (1S)-2,3,4,6-tetra-O-acetyl-1,5-anhydro-1-[3-(1-benzothien-2-ylmethyl)-4-fluorophenyl]glucitol (76.9 kg) was added a water (230 liters) solution of sodium hydroxide (26.9 kg) at a temperature of 25° C. or lower, followed by stirring at 40.0 to 49.1° C. for 4 hours. Water (850 liters) was added to the reaction mixture, and 12.9 kg of 38% hydrochloric acid was added thereto at a temperature of 25° C. or lower. The mixture was heated to 60° C., followed by stirring at 20.2 to 25.0° C. for 9.5 hours. The separated-out crystals were collected by filtration, washed with tap water (80 liters), and vacuum-dried to obtain, as white crystals, (1S)-1,5-anhydro-1-C-[3-(1-benzothiophene-2-ylmethyl)-4-fluorophenyl]-D-glucitol [52.7 kg, yield: 97.0%, purity: 99% (HPLC)].

Workup

additionwas added
customat a temperature of 25° C.
temperatureThe mixture was heated to 60° C.
stirringby stirring at 20.2 to 25.0° C. for 9.5 hours
filtrationThe separated-out crystals were collected by filtration
washwashed
customvacuum-dried

Sources & evidence

ORD record: ord-aca7cc9f89de40279816333ba8b48a0c
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08198464B2

Reaction notes

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