Hydrochloric Acid → 1,3-Thiazol-5-ylmethyl N-((1S,2S,4S)-4-amino-1-benzyl-2-hydroxy-5-phenylpentyl)carbamate

HRID 865801Notes

Reaction equation

HRID 865801 reaction equation
[NH2:1][C@H:2]([C@@H:10]([OH:28])[CH2:11][C@@H:12]([NH:20]C(OC(C)(C)C)=O)[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl.[N+](C1C=CC(O[C:40]([O:42][CH2:43][C:44]2[S:48][CH:47]=[N:46][CH:45]=2)=[O:41])=CC=1)([O-])=O.C(=O)(O)[O-].[Na+].O.N.Cl>C(OCC)(=O)C.O>[NH2:20][C@@H:12]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH2:11][C@H:10]([OH:28])[C@@H:2]([NH:1][C:40]([O:42][CH2:43][C:44]1[S:48][CH:47]=[N:46][CH:45]=1)=[O:41])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 119979265-tert-Butyloxycarbonylamino-2-amino-3-hydroxy-1,6-diphenylhexane, (2S,3S,5S)-HCID 12896473Azane;hydrateHCID 218783405-Hydroxymethylthiazole 4-nitrophenylcarbonate hydrochloride

Product 1

HCID 111019781,3-Thiazol-5-ylmethyl N-((1S,2S,4S)-4-amino-1-benzyl-2-hydroxy-5-phenylpentyl)carbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
30 °C

Procedure

To a 750 gallon glass lined reactor were charged (2S, 3S, 5S)-2-Amino-3-hydroxy-5-(t-butyloxycarbonylamino)-1,6-diphenylhexane--0.5succinic acid salt (75.0 kg, 169 moles), 5-(p-nitrophenyloxycarbonyloxymethyl)thiazole hydrochloride (65.0 kg, 205 moles) and sodium bicarbonate (70.0 kg, 833 moles). Ethyl acetate (826 kg, 918 L) was added and the agitator was started. Tap water (788 kg) was added and the mixture was warmed to 30° C. and stirred for 2.5 hours until all of the solids were dissolved. After settling for 30 minutes, the aqueous layer was separated and discarded. The organic layer was warmed to 60° C. and stirred for 12 hours. The solution was then cooled to 30° C. and 28% ammonia water (9.0 kg, 148 moles) was added. The mixture was stirred for 3 hours at 25°-30° C. The mixture was washed three times with aqueous 10% potassium carbonate solution (903 kg each time). The aqueous layers were drained and discarded after each wash. Concentrated hydrochloric acid (59.0 kg, 600 moles) was added to the ethyl acetate solution and warmed to 50° C. with stirring for 3 hours.

Workup

  1. additionwas added
  2. dissolutionwere dissolved
  3. waitAfter settling for 30 minutes
  4. customthe aqueous layer was separated
  5. temperatureThe organic layer was warmed to 60° C.
  6. stirringstirred for 12 hours
  7. temperatureThe solution was then cooled to 30° C.
  8. stirringThe mixture was stirred for 3 hours at 25°-30° C
  9. washThe mixture was washed three times with aqueous 10% potassium carbonate solution (903 kg each time)
  10. temperaturewarmed to 50° C.
  11. stirringwith stirring for 3 hours

Sources & evidence

ORD record
ord-62a3d21795954573bf0988790c4ad5ec
Source dataset
uspto-grants-1996_10
Patent number
US05567823

Reaction notes

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