Acetonitrile → (1,3-DIoxoisoindol-2-yl)(4-fluorophenyl)acetic acid

HRID 1531855

Reaction equation

HRID 1531855 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5](NCC(O)=O)=[CH:4][CH:3]=1.[C:13](=[O:16])([O-])[O-:14].[Na+].[Na+].C(#N)C.[C:22]([N:27]1[C:31](=[O:32])[C:30]2=[CH:33][CH:34]=[CH:35][CH:36]=[C:29]2[C:28]1=[O:37])(OCC)=O>O>[C:28]1(=[O:37])[N:27]([CH:22]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[C:13]([OH:14])=[O:16])[C:31](=[O:32])[C:30]2=[CH:33][CH:34]=[CH:35][CH:36]=[C:29]12

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 10340Sodium CarbonateHCID 31187N-CarbethoxyphthalimideHCID 1133296(4-Fluoroanilino)acetic acid

Product 1

HCID 9904369(1,3-DIoxoisoindol-2-yl)(4-fluorophenyl)acetic acidYield 76%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a stirred solution of 4-fluorophenylglycine (3.38 g, 20.0 mmol) and sodium carbonate in 450 mL of 2:1 water:acetonitrile is added N-carbethoxyphthalimide (4.38 g, 20 mmol). After 1 hour, the reaction mixture is partially concentrated to remove the acetonitrile. The resulting slurry is filtered and the pH of the stirred filtrate is adjusted to 1-2 with 4 N hydrochloric acid and then stirred for an additional 30 minutes and filtered. The solid is air-dried and then dried in vacuo (60° C., <1 mm) to afford 4.55 g (76%) of α-phthalimido4-fluorophenylacetic acid as a white powder: mp 180-183° C.; 1H NMR (DMSO-d6, 250 MHz) δ8.10-7.80 (m, 4H), 7.65-7.45 (m, 4H), 7.3-7.10 (t, 2 H) 610 (s, 1H); 13C NMR (DMSO-d6, 250 MHz) δ168.9, 166.9, 163.6, 159.7, 135.0, 131.4, 131.3 (m), 130.9, 123.5, 115.0, 114.7, 54.4. Anal. Calculated for C16H10NO4F. Theoretical: C, 64.22; H, 3.37; N, 4.68. Found: C, 64.13; H, 3.33; N, 4.63.

Workup

  1. concentrationthe reaction mixture is partially concentrated
  2. customto remove the acetonitrile
  3. filtrationThe resulting slurry is filtered
  4. filtrationfiltered
  5. customThe solid is air-dried
  6. customdried in vacuo (60° C., <1 mm)

Sources & evidence

ORD record
ord-7f9e6a09dbe84e71af2673b197eb7788
Source dataset
uspto-grants-2001_03
Patent number
US06200987B1

Linked notes

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