Water → [(3S)-6-({2',6'-dimethyl-4'-[3-(methylsulfonyl)propoxy]biphenyl-3-yl}methoxy)-2,3-dihydro-1-benzofuran-3-yl]acetic acid hydrate

HRID 1848784Notes

Reaction equation

HRID 1848784 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][CH2:10][CH2:11][S:12]([CH3:15])(=[O:14])=[O:13])[CH:5]=[C:4]([CH3:16])[C:3]=1[C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH2:23][O:24][C:25]2[CH:37]=[CH:36][C:28]3[C@H:29]([CH2:32][C:33]([OH:35])=[O:34])[CH2:30][O:31][C:27]=3[CH:26]=2)[CH:18]=1.O>CC(C)=O>[OH2:8].[CH3:16][C:4]1[CH:5]=[C:6]([O:8][CH2:9][CH2:10][CH2:11][S:12]([CH3:15])(=[O:14])=[O:13])[CH:7]=[C:2]([CH3:1])[C:3]=1[C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH2:23][O:24][C:25]2[CH:37]=[CH:36][C:28]3[C@H:29]([CH2:32][C:33]([OH:35])=[O:34])[CH2:30][O:31][C:27]=3[CH:26]=2)[CH:18]=1

Participants

4

Reactant 2

HCID 962Water2×HCID 24857286Fasiglifam

Product 1

HCID 46869922[(3S)-6-({2',6'-dimethyl-4'-[3-(methylsulfonyl)propoxy]biphenyl-3-yl}methoxy)-2,3-dihydro-1-benzofuran-3-yl]acetic acid hydrateYield 173.7%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

[(3S)-6-({2′,6′-Dimethyl-4′-[3-(methylsulfonyl)propoxy]biphenyl-3-yl}methoxy)-2,3-dihydro-1-benzofuran-3-yl]acetic acid (212.60 g) was dissolved in acetone (510 mL). Water (255 mL) was added dropwise. Seed crystal was added, and the mixture was stirred for 2 hr. The mixture was cooled to 10° C. or below, and stirred for 2 hr. While cooling to 10° C. or below, water (765 mL) was added dropwise, and the mixture was stirred for 2 hr. The precipitated solid was collected by filtration, and washed with a mixed solution (1360 mL) of acetone.water (1:4). The obtained solid was dried at 50° C. under reduced pressure to give [(3S)-6-({2′,6′-dimethyl-4′-[3-(methylsulfonyl)propoxy]biphenyl-3-yl}methoxy)-2,3-dihydro-1-benzofuran-3-yl]acetic acid hydrate as crystals (190.94 g). 100% ee.

Workup

  1. additionSeed crystal was added
  2. temperatureThe mixture was cooled to 10° C. or below
  3. stirringstirred for 2 hr
  4. temperatureWhile cooling to 10° C. or below
  5. stirringthe mixture was stirred for 2 hr
  6. filtrationThe precipitated solid was collected by filtration
  7. washwashed with a mixed solution (1360 mL) of acetone
  8. customThe obtained solid was dried at 50° C. under reduced pressure

Sources & evidence

ORD record
ord-45f5e288b95c402b8969c8fe3f9fbf14
Source dataset
uspto-grants-2015_02
Patent number
US08952185B2

Reaction notes

Loading…