Hydrochloric Acid → HCID 131711280, compound

HRID 1764787Notes

Reaction equation

HRID 1764787 reaction equation
CCOCC.Cl.[NH2:7][C@H:8]([C:20]([NH:22][C@H:23]([C:34]([NH:36][C@H:37]([C:47]([NH:49][C@H:50]([C:60]([NH:62][C@H:63]([C:76]([OH:78])=[O:77])[CH2:64][CH2:65][C:66](=[O:75])[O:67][CH2:68][C:69]1[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=1)=[O:61])[CH2:51][O:52][CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)=[O:48])[CH2:38][O:39][CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[O:35])[C@@H:24]([CH3:33])[O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:21])[CH2:9][C:10](=[O:19])[O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[NH:79]([C:94]([O:96][C:97]([CH3:100])([CH3:99])[CH3:98])=[O:95])[C@H:80]([C:84](ON1C(=O)CCC1=O)=[O:85])[CH:81]([CH3:83])[CH3:82]>C1COCC1.CN(C=O)C.CCN(CC)CC>[NH:79]([C:94]([O:96][C:97]([CH3:99])([CH3:98])[CH3:100])=[O:95])[C@H:80]([C:84]([NH:7][C@H:8]([C:20]([NH:22][C@H:23]([C:34]([NH:36][C@H:37]([C:47]([NH:49][C@H:50]([C:60]([NH:62][C@H:63]([C:76]([OH:78])=[O:77])[CH2:64][CH2:65][C:66](=[O:75])[O:67][CH2:68][C:69]1[CH:70]=[CH:71][CH:72]=[CH:73][CH:74]=1)=[O:61])[CH2:51][O:52][CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)=[O:48])[CH2:38][O:39][CH2:40][C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1)=[O:35])[C@@H:24]([CH3:33])[O:25][CH2:26][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)=[O:21])[CH2:9][C:10](=[O:19])[O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:85])[CH:81]([CH3:82])[CH3:83]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 98768Boc-Val-osuHCID 131711281HCID 131711281, compound

Product 1

HCID 131711280HCID 131711280, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent2×

Procedure

Boc-Asp(OBzl)-Thr(Bzl)-Ser(Bzl)-Ser(Bzl)-Glu(OBzl)-OH (50.0 g, 46 mmol) was deprotected with HCl (4.15 N) in THF and worked up as usual to give 45.4 g of white solid. It was dissolved in THF (1.5 liters) and treated with ether (7 liters). On standing at 0° overnight a white solid powder was obtained (44.0 g, mp 179°-184°). Part of this material, HCl.H-Asp(OBzl)-Thr(Bzl)-Ser(Bzl)-Ser(Bzl)-Glu(OBzl)-OH (43.7 g, 42.7 mmol) was then dissolved in 500 ml of DMF, cooled to 0°, and treated with Boc-Val-OSu (15.4 g, 49 mmol) and Et3N (10 ml). The mixture was stirred for 15 hours during which time more Et3N (7.9 ml) was added in several portions maintaining the reaction slightly basic. The insoluble matter was removed by filtration and the filtrate evaporated to dryness. The oily residue was dissolved in CH2Cl2, washed with 5% HOAc, H2O, dried (Na2SO4), and evaporated to a smaller volume (0.5 liter) when treated with petroleum ether. The product crystallized slowly during overnight standing. It was recrystallized from THF and i-PrOH to yield, 26.3 g (51.4%); mp 174°-177°; [α]D25 = +0.84° (c l, THF).

Workup

  1. customa white solid powder was obtained (44.0 g, mp 179°-184°)
  2. temperaturecooled to 0°
  3. additionwas added in several portions
  4. temperaturemaintaining
  5. customthe reaction slightly basic
  6. customThe insoluble matter was removed by filtration
  7. customthe filtrate evaporated to dryness
  8. dissolutionThe oily residue was dissolved in CH2Cl2
  9. washwashed with 5% HOAc, H2O
  10. dry with materialdried (Na2SO4)
  11. customevaporated to a smaller volume (0.5 liter) when
  12. additiontreated with petroleum ether
  13. customThe product crystallized slowly during overnight
  14. customIt was recrystallized from THF and i-PrOH
  15. customto yield

Sources & evidence

ORD record
ord-d866fa723e1646a0a2ae8ee3a8f08c41
Source dataset
uspto-grants-1978_09
Patent number
US04116951

Reaction notes

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