4-Methylmorpholine → Boc-Val-Leu-Pro-OBn

HRID 2243827Notes

Reaction equation

[CH3:1][CH:2]([C@H:4]([NH:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[C:5]([OH:7])=O)[CH3:3].CN1CCOCC1.[NH2:23][C@H:24]([C:29]([N:31]1[CH2:45][CH2:44][CH2:43][C@H:32]1[C:33]([O:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[O:34])=[O:30])[CH2:25][CH:26]([CH3:28])[CH3:27].C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>C(Cl)Cl.CCOC(C)=O>[NH:8]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[C@H:4]([C:5]([NH:23][C@H:24]([C:29]([N:31]1[CH2:45][CH2:44][CH2:43][C@H:32]1[C:33]([O:35][CH2:36][C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1)=[O:34])=[O:30])[CH2:25][CH:26]([CH3:27])[CH3:28])=[O:7])[CH:2]([CH3:1])[CH3:3]

Participants

Conditions

Temperature: 23 °C

Procedure

To a flask containing Boc-Valine-OH (652 mg, 3 mmol) in DCM (6 ml) at 0° C. was added NMM (0.35 ml, 3.15 mmol). After stirring for 15 min, A5 (1.065 g, 3 mmol), HOBt (405 mg, 3.0 mmol) and DCC (650 mg, 3.15 mmol) were added in portions. The reaction mixture was allowed to warm to 23° C. and stirred for 14 h. The suspension was diluted with DCM (25 ml) and washed successively with aq KHSO4 (2×10 ml, 10%), aq NaHCO3 (2×10 ml, sat) and brine (10 ml) dried over Na2SO4 filtered and concentrated under reduced pressure. The residue was purified by flash LC (silica, gradient hex-EtOAc 2:1 to 1:1) to give SVPLA4 (1.48 g, 93%) as a white solid. Rf=0.57 (hex-EtOAc 1:2).

Workup

stirringstirred for 14 h
washwashed successively with aq KHSO4 (2×10 ml, 10%), aq NaHCO3 (2×10 ml, sat) and brine (10 ml)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe residue was purified by flash LC (silica, gradient hex-EtOAc 2:1 to 1:1)
customto give SVPLA4 (1.48 g, 93%) as a white solid

Sources & evidence

ORD record: ord-00df25e4d1c94ac0a2aeb9f1b30ce02b
Source dataset: uspto-grants-2010_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07678765B2

Reaction notes

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