Chlorosuccinimide → tert-butyl N-[[4-[(Z)-C-chloro-N-hydroxycarbonimidoyl]phenyl]methyl]-N-(oxan-4-yl)carbamate

HRID 575911Notes

Reaction equation

HRID 575911 reaction equation
[OH:1]/[N:2]=[CH:3]/[C:4]1[CH:24]=[CH:23][C:7]([CH2:8][N:9]([CH:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[CH:6][CH:5]=1.[Cl:25]N1C(=O)CCC1=O>C(OC(C)=O)(C)C.O>[Cl:25]/[C:3](=[N:2]\[OH:1])/[C:4]1[CH:5]=[CH:6][C:7]([CH2:8][N:9]([CH:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[CH:23][CH:24]=1

Participants

5

Reactant 2

HCID 31398ChlorosuccinimideHCID 88996068tert-butyl N-[[4-[(E)-hydroxyiminomethyl]phenyl]methyl]-N-(oxan-4-yl)carbamate

Product 1

HCID 88996291tert-butyl N-[[4-[(Z)-C-chloro-N-hydroxycarbonimidoyl]phenyl]methyl]-N-(oxan-4-yl)carbamateYield 89%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 7915Isopropyl AcetateSolvent

Conditions

Temperature
20 °C

Procedure

A suspension of (E)-tert-butyl 4-((hydroxyimino)methyl)benzyl(tetrahydro-2H-pyran-4-yl)carbamate (A-4) (1662 g, 4.97 mol) in i-PrOAc (16.6 L) is stirred at 20° C. in a reactor. N-chlorosuccinimide (730 g, 5.47 mol) is added maintaining about 20° C. The suspension is stirred at about 20° C. to complete the reaction. The suspension is diluted with water (8.3 L) and stirred to dissolve the solid. The phases are separated and the organic phase is washed with water (8.3 L). The organic phase is concentrated then diluted with i-PrOAc (831 mL). Heptane (13.3 L; 8 V) is slowly added to induce crystallization. The thick suspension is then stirred for 1 h. The solid is collected by filtration; the filter-cake is washed with heptane (2×1.6 L; 2×1 V) and dried to afford (Z)-tert-butyl 4-(chloro(hydroxyimino)methyl)benzyl(tetrahydro-2H-pyran-4-yl)carbamate (A-4-i) (1628 g; 89%, 98.0 area % purity by HPLC) as a white powder.

Workup

  1. temperaturemaintaining about 20° C
  2. stirringThe suspension is stirred at about 20° C.
  3. customthe reaction
  4. stirringstirred
  5. dissolutionto dissolve the solid
  6. customThe phases are separated
  7. washthe organic phase is washed with water (8.3 L)
  8. concentrationThe organic phase is concentrated
  9. additionthen diluted with i-PrOAc (831 mL)
  10. additionHeptane (13.3 L; 8 V) is slowly added
  11. customcrystallization
  12. stirringThe thick suspension is then stirred for 1 h
  13. filtrationThe solid is collected by filtration
  14. washthe filter-cake is washed with heptane (2×1.6 L; 2×1 V)
  15. customdried

Sources & evidence

ORD record
ord-d3d510ec53cf4eac8c8c770bd7fed684
Source dataset
uspto-grants-2015_05
Patent number
US09035053B2

Reaction notes

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