Triethylamine → HCID 10893933, compound

HRID 1108119Notes

Reaction equation

HRID 1108119 reaction equation
[C:1]([NH:8][CH2:9][C:10]([OH:12])=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C(N(CC)CC)C.C(Cl)(=O)C(C)(C)C.Cl.[C:28]1([CH2:34][C:35]([NH2:43])([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH3:36])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>ClCCl>[C:4]([O:3][C:1]([NH:8][CH2:9][C:10]([NH:43][C:35]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)([CH3:36])[CH2:34][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:12])=[O:2])([CH3:5])([CH3:6])[CH3:7]

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 62493Pivaloyl chlorideHCID 78288N-(tert-butoxycarbonyl)glycineHCID 19907804149756-73-0

Product 1

HCID 10893933HCID 10893933, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A reaction vessel was charged with dichloromethane (360 l) and Boc-glycine (32.6 kg, 186.3 mol). Triethylamine (18.8 kg, 186.1 mol) was added cautiously keeping the temperature below 25° C. The mixture was cooled to below -5° C. and pivaloyl chloride (trimethylacetyl chloride, 22.4 kg, 185.9 mol) in dichloromethane (40 l) was added at such a rate as to keep the temperature below -5° C. This was washed in with dichloromethane (2 l). The mixture was then stirred at below -5° C. for 2-2.5 h and then 1,2-diphenyl-2-propylamine hydrochloride (40 kg, 161.1 mol, dry weight estimate, actual weight including moisture 42.94 kg) was added as a solid through the manway keeping the temperature below -5° C. Triethylamine (28.4 kg, 281.2 mol) was then added keeping the temperature below -5° C. This was washed in with dichloromethane (2 l). The mixture was stirred at below -5° C. for 2.75-3.25 h, water (400 l) was added and the mixture stirred for at least 15 min. The organic layer was separated and washed with dilute hydrochloric acid made up from concentrated hydrochloric acid (40 l) and water (400 l). The organic layer was again separated and then about 80% (360 l) of the dichloromethane was removed by distillation. Isopropyl alcohol (140 l) was then charged and distillation continued until the head temperature reached 80° C. The solution was then cooled and isopropyl alcohol added to make up to a total weight of 200 kg. This solution was then divided in two by weight and each half used directly in the next step.

Workup

  1. customthe temperature below 25° C
  2. temperatureThe mixture was cooled to below -5° C.
  3. customthe temperature below -5° C
  4. washThis was washed in with dichloromethane (2 l)
  5. customthe temperature below -5° C
  6. customthe temperature below -5° C
  7. washThis was washed in with dichloromethane (2 l)
  8. stirringThe mixture was stirred at below -5° C. for 2.75-3.25 h
  9. additionwater (400 l) was added
  10. stirringthe mixture stirred for at least 15 min
  11. customThe organic layer was separated
  12. washwashed with dilute hydrochloric acid
  13. customThe organic layer was again separated
  14. customabout 80% (360 l) of the dichloromethane was removed by distillation
  15. additionIsopropyl alcohol (140 l) was then charged
  16. distillationdistillation
  17. customreached 80° C
  18. temperatureThe solution was then cooled
  19. additionisopropyl alcohol added

Sources & evidence

ORD record
ord-67f68862495f4e78acb0917bae974862
Source dataset
uspto-grants-2000_05
Patent number
US06063962

Reaction notes

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