Diisopropylethylamine → N-tert-butoxycarbonyl O-allyl L-seryl L-valyl L-valyl O-allyl L-seryl glycine methyl ester

HRID 2370903Notes

Reaction equation

HRID 2370903 reaction equation
FC(F)(F)C(O)=O.[CH3:8][O:9][C:10](=[O:22])[CH2:11][NH:12][C:13](=[O:21])[C@H:14]([CH2:16][O:17][CH2:18][CH:19]=[CH2:20])[NH2:15].[C:23]([O:27][C:28]([NH:30][C@H:31]([C:37]([NH:39][C@H:40]([C:44]([NH:46][C@H:47]([C:51](O)=[O:52])[CH:48]([CH3:50])[CH3:49])=[O:45])[CH:41]([CH3:43])[CH3:42])=[O:38])[CH2:32][O:33][CH2:34][CH:35]=[CH2:36])=[O:29])([CH3:26])([CH3:25])[CH3:24].C(N(CC)C(C)C)(C)C.C1C=C2N=NN(O)C2=CC=1.O.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl>[CH3:8][O:9][C:10](=[O:22])[CH2:11][NH:12][C:13](=[O:21])[C@H:14]([CH2:16][O:17][CH2:18][CH:19]=[CH2:20])[NH:15][C:51](=[O:52])[C@H:47]([CH:48]([CH3:50])[CH3:49])[NH:46][C:44](=[O:45])[C@H:40]([CH:41]([CH3:42])[CH3:43])[NH:39][C:37](=[O:38])[C@H:31]([CH2:32][O:33][CH2:34][CH:35]=[CH2:36])[NH:30][C:28]([O:27][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:29]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 86671352N-tert-butoxycarbonyl O-allyl L-seryl L-valyl L-valineHCID 86671357O-allyl L-seryl glycine methyl ester trifluoroacetate

Product 1

HCID 86671359N-tert-butoxycarbonyl O-allyl L-seryl L-valyl L-valyl O-allyl L-seryl glycine methyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

O-allyl L-seryl methyl ester trifluoroacetate 20 (7.03 g, 21.3 mmol), N-tert-butoxycarbonyl O-allyl L-seryl L-valyl L-valine 15 (9.45 g, 21.3 mmol) and N,N-diisopropylethyl amine (2.75 g, 21.3 mmol) were dissolved in CH2Cl2 (100 mL) and the solution cooled to 0° C. (icebath). HOBt hydrate (3.26 g, 21.3 mmol) and then EDC hydrochloride (4.49 g, 23.4 mmol) were added in small portions. The reaction mixture was stirred for 1 h 30 min at 0° C. after which the icebath was removed and the mixture stirred for 14 h 30 min. The volume was then increased by addition of CH2Cl2 (200 mL) and the mixture stirred for another 7 hours before the volume was increased to 400 mL. The suspension was washed with 2M aqueous H2SO4 (150+300+450 mL), 7.5% (w/w) aqueous K2CO3 (150+300+450 mL), saturated brine (400 mL) and water (400+600 mL). The suspension was then diluted with CH2Cl2 (1.5 L) and dried with 3 Å molecular sieves resulting in a slightly turbid solution.

Workup

  1. customwas removed
  2. stirringthe mixture stirred for 14 h 30 min
  3. temperatureThe volume was then increased by addition of CH2Cl2 (200 mL)
  4. stirringthe mixture stirred for another 7 hours before the volume
  5. temperaturewas increased to 400 mL
  6. washThe suspension was washed with 2M aqueous H2SO4 (150+300+450 mL), 7.5% (w/w) aqueous K2CO3 (150+300+450 mL), saturated brine (400 mL) and water (400+600 mL)
  7. additionThe suspension was then diluted with CH2Cl2 (1.5 L)
  8. customdried with 3 Å molecular sieves
  9. customresulting in a slightly turbid solution

Sources & evidence

ORD record
ord-2725f7b543e24607a3049b2c7bec4a4d
Source dataset
uspto-grants-2014_04
Patent number
US08710008B2

Reaction notes

Loading…