Sodium Hydroxide → HCID 10204543, compound

HRID 1883707Notes

Reaction equation

HRID 1883707 reaction equation
[C:1]1([CH3:21])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]1[O:9][C:10]2[CH:16]=[C:15]([CH2:17][C:18]([OH:20])=O)[CH:14]=[CH:13][C:11]=2[N:12]=1.C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)O.[NH2:46][C:47]1[CH:48]=[C:49]2[C:53](=[CH:54][CH:55]=1)[CH2:52][CH:51]([CH2:56][C:57]([O:59]CC)=[O:58])[CH2:50]2.[OH-].[Na+]>CN(C)C=O>[CH4:1].[C:1]1([CH3:21])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]1[O:9][C:10]2[CH:16]=[C:15]([CH2:17][C:18]([NH:46][C:47]3[CH:48]=[C:49]4[C:53](=[CH:54][CH:55]=3)[CH2:52][CH:51]([CH2:56][C:57]([OH:59])=[O:58])[CH2:50]4)=[O:20])[CH:14]=[CH:13][C:11]=2[N:12]=1

Participants

8

Reactant 5

HCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 21864398Tetramethyluronium hexafluorophosphateHCID 235083152-(2-(O-tolylamino)benzo[d]oxazol-6-yl)acetic acidHCID 86590038HCID 86590038, compound

Product 2

HCID 297MethaneHCID 10204543HCID 10204543, compoundYield 9.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A stirred solution of (2-o-tolylamino-benzoxazol-6-yl)-acetic acid (0.64 g, Reference Example 2) in dimethylformamide (5 mL) was treated successively with diisopropylethylamine (0.59 g), O-7-azabenzotriazol-1-yl)-1,1,3,3,-tetramethyluronium hexafluorophosphate (0.95 g), and a solution of ethyl (5-amino-indan-2-yl)-acetate [0.5 g, Reference Example 8(a)] in dimethylformamide (2.5 mL). After stirring at room temperature overnight the reaction was evaporated and the residual oil was dissolved in ethyl acetate. The ethyl acetate solution was washed twice with dilute hydrochloric acid, then with aqueous sodium bicarbonate, then with water and then evaporated. The residue was dissolved in industrial methylated spirits (100 mL) and the solution was treated with 3 equivalents of aqueous sodium hydroxide. After stirring at room temperature overnight (HPLC showed that none of the intermediate ester remained) the reaction mixture was evaporated. The residue was partitioned between ethyl acetate and water (with the pH of the aqueous layer adjusted to 2 by addition of dilute hydrochloric acid). The organic phase was dried over magnesium sulfate then evaporated. The residual brown gum was recrystallised from a mixture of acetonitrile and water at pH 2, then from acetonitrile after treatment with charcoal to give the title compound (0.050 g). LC-MS: RT=3.21 minutes (100% by ELSD); MS(ES+) 456(MH+).

Workup

  1. customwas evaporated
  2. dissolutionthe residual oil was dissolved in ethyl acetate
  3. washThe ethyl acetate solution was washed twice with dilute hydrochloric acid
  4. customwith aqueous sodium bicarbonate, then with water and then evaporated
  5. dissolutionThe residue was dissolved in industrial methylated spirits (100 mL)
  6. stirringAfter stirring at room temperature overnight (HPLC
  7. customwas evaporated
  8. customThe residue was partitioned between ethyl acetate and water (with the pH of the aqueous layer
  9. additionadjusted to 2 by addition of dilute hydrochloric acid)
  10. dry with materialThe organic phase was dried over magnesium sulfate
  11. customthen evaporated
  12. customThe residual brown gum was recrystallised from a mixture of acetonitrile and water at pH 2

Sources & evidence

ORD record
ord-d3f3d7924eb74915b91b5a5d32bee1b5
Source dataset
uspto-grants-2004_07
Patent number
US06762199B2

Reaction notes

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