Acetic Acid → SB202235

HRID 1376896Notes

Reaction equation

HRID 1376896 reaction equation
[CH2:1]([O:8][C:9]1[CH:19]=[CH:18][C:12]2[C@H:13]([NH:16][OH:17])[CH2:14][O:15][C:11]=2[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[N:21]([CH:23]=[O:24])C.C(O)(=O)C.[O-]C#N.[K+]>O>[CH2:1]([O:8][C:9]1[CH:19]=[CH:18][C:12]2[C@H:13]([N:16]([OH:17])[C:23]([NH2:21])=[O:24])[CH2:14][O:15][C:11]=2[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 6228DimethylformamideHCID 11076092HCID 11076092, compoundHCID 11378442Potassium cyanate

Product 1

HCID 153939SB202235Yield 83%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

To a stirred solution of (S)-N-(6-benzyloxy-2,3-dihydrobenzofuran-3-yl)hydroxyamine of Example 7(b) above, (10.0 kg, 38.9 moles), DMF (50.0 L), and acetic acid (3.34 L) cooled to 5° C. was added in one portion, a cooled (0° C.) solution of potassium cyanate (4.73 kg, 58.3 moles) in water (9.0 L). This was added at such a rate that the internal temperature did not exceed 10° C. The resultant suspension was stirred for 30 min at room temperature. Water (213 L) was added and the mixture stirred for 1 hour at ambient temperature. The product was collected by centrifugation and the wet cake washed with water (425 L) and 95% ethanol (40 L). The product was isolated an dried at 45°-50° C. under vacuum to afford the crude product (11.4, 97%) as an off white solid. The crude product (11.0 kg) was recrystallized from DMF/TBME (110 L/233 L)) and washed with TBME (89 L) to afford the desired compound (9.1 kg, 83%) as a white solid after drying at 45°-50° C. under vacuum. The product was greater than 99% e.e. as determined by chiral HPLC.

Workup

  1. additionwas added in one portion
  2. additionThis was added at such a rate that the internal temperature
  3. customdid not exceed 10° C
  4. customThe product was collected by centrifugation
  5. washthe wet cake washed with water (425 L) and 95% ethanol (40 L)
  6. customThe product was isolated
  7. customan dried at 45°-50° C. under vacuum
  8. customto afford the crude product (11.4, 97%) as an off white solid
  9. customThe crude product (11.0 kg) was recrystallized from DMF/TBME (110 L/233 L)) and
  10. washwashed with TBME (89 L)

Sources & evidence

ORD record
ord-0b64a74167794b26854c977a18746858
Source dataset
uspto-grants-1997_09
Patent number
US05663368

Reaction notes

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