4-Toluenesulfonyl chloride → di-tert-butyl 4-{3-{[(4-methylphenyl)sulfonyl)oxy]propyl}-N-trityl-L-glutamate

HRID 1466548Notes

Reaction equation

C(N(CC)CC)C.[CH3:8][C:9]1[CH:14]=[CH:13][C:12]([S:15](Cl)(=[O:17])=[O:16])=[CH:11][CH:10]=1.[OH:19][CH2:20][CH2:21][CH2:22][CH:23]([C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[CH2:24][C@@H:25]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[NH:26][C:27]([C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>ClCCl>[CH3:8][C:9]1[CH:14]=[CH:13][C:12]([S:15]([O:19][CH2:20][CH2:21][CH2:22][CH:23]([C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[CH2:24][C@@H:25]([C:46]([O:48][C:49]([CH3:51])([CH3:52])[CH3:50])=[O:47])[NH:26][C:27]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)(=[O:17])=[O:16])=[CH:11][CH:10]=1

Participants

Conditions

Temperature: 0 °C

Procedure

At 0° C. triethylamine (0.31 mL, 2.2 mmol) and 4-methylbenzenesulfonyl chloride (0.141 g, 0.74 mmol) were added to a solution of di-tert-butyl 4-(3-hydroxypropyl)-N-trityl-L-glutamate (0.239 g, 0.427 mmol) in dichloromethane (10 mL). The resulting mixture was stirred at 0° C. for 2 h and for 16 h at room temperature. The solution was concentrated and the crude product was purified by flash chromatography (silica, ethyl acetate/hexane) to afford di-tert-butyl 4-{3-{[(4-methylphenyl)sulfonyl)oxy]propyl}-N-trityl-L-glutamate (0.255 mg, 67%) as a mixture of (4S,4S)/(2S,4R) diastereoisomers. The isomers were separated by chiral HPLC (Chiralpak AD-H 5 μm 250×20 mm, hexane/2-propanol 9:1, 25 mL/min):

Workup

concentrationThe solution was concentrated
customthe crude product was purified by flash chromatography (silica, ethyl acetate/hexane)

Sources & evidence

ORD record: ord-15e045637b734f7bae7811b5d74a53eb
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09000037B2

Reaction notes

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