Triethylamine → BOC-Asn-Leu-Ser-Thr-OBzl

HRID 971581Notes

Reaction equation

HRID 971581 reaction equation
[NH:1]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C@H:2]([C:7]([OH:9])=O)[CH2:3][C:4](=[O:6])[NH2:5].CC[N+]1OC(C2C=CC=C(S([O-])(=O)=O)C=2)=CC=1.C(N(CC)CC)C.[NH2:41][C@H:42]([C:47]([NH:49][C@H:50]([C:53]([NH:55][C@H:56]([C:60]([O:62][CH2:63][C:64]1[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=1)=[O:61])[C@@H:57]([CH3:59])[OH:58])=[O:54])[CH2:51][OH:52])=[O:48])[CH2:43][CH:44]([CH3:46])[CH3:45].FC(C(O)=O)(F)F>C(#N)C.CN(C)C=O>[NH:1]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C@H:2]([C:7]([NH:41][C@H:42]([C:47]([NH:49][C@H:50]([C:53]([NH:55][C@H:56]([C:60]([O:62][CH2:63][C:64]1[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=1)=[O:61])[C@@H:57]([CH3:59])[OH:58])=[O:54])[CH2:51][OH:52])=[O:48])[CH2:43][CH:44]([CH3:46])[CH3:45])=[O:9])[CH2:3][C:4](=[O:6])[NH2:5]

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 77804Woodward's reagent KHCID 82035N2-((tert-Butoxy)carbonyl)-L-asparagineHCID 131710003H-Leu-Ser-Thr-OBzl.TFA

Product 1

HCID 131710002BOC-Asn-Leu-Ser-Thr-OBzl

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
20 °C

Procedure

20.8 g of BOC-Asn-OH are suspended in 208 ml of acetonitrile, mixed with 22.7 g of Woodward's Reagent K and the mixture stirred for 30 minutes at 20° C. 12.6 ml of triethylamine are then added dropwise, whilst stirring, in such a way that the internal temperature does not exceed +32° C., and the mixture is cooled to 20° C. and stirred for a further 50 minutes at this temperature. The almost clear solution is cooled to 0° C. and is mixed with a solution, also cooled to 0° C., of 39.1 g of H-Leu-Ser-Thr-OBzl.TFA and 10.5 ml of triethylamine in 257 ml of dimethylformamide. The reaction mixture, which soon solidifies, is stirred overnight at room temperature, cooled to -10° C. and stirred for a further 2 hours at -10° C. Thereafter the crystalline precipitate is filtered off and the tetrapeptide derivative is washed once with cold acetonitrile, once with ethyl acetate and three times with water until it is free of chloride. The resulting product is crystallised from 370 ml of dimethylformamide, 3.7 ml of glacial acetic acid and 370 ml of acetonitrile. Melting point 225°-226° C.; [α]D = -36° (c = 2 in dimethylformamide); Rf6 = 0.85 (on silica gel).

Workup

  1. stirringwhilst stirring
  2. customdoes not exceed +32° C.
  3. temperaturethe mixture is cooled to 20° C.
  4. stirringstirred for a further 50 minutes at this temperature
  5. temperatureThe almost clear solution is cooled to 0° C.
  6. additionis mixed with a solution
  7. stirringis stirred overnight at room temperature
  8. temperaturecooled to -10° C.
  9. stirringstirred for a further 2 hours at -10° C
  10. filtrationThereafter the crystalline precipitate is filtered off
  11. washthe tetrapeptide derivative is washed once with cold acetonitrile, once with ethyl acetate and three times with water until it
  12. customThe resulting product is crystallised from 370 ml of dimethylformamide, 3.7 ml of glacial acetic acid and 370 ml of acetonitrile

Sources & evidence

ORD record
ord-d7b014116a0742dda512e9efdc107583
Source dataset
uspto-grants-1979_07
Patent number
US04159981

Reaction notes

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