Acetic Acid → n-Hydroxy-4-benzyloxycarbonyl-1-{4-[5-fluoroindol-3-yl]piperidine-1-sulfonyl}piperazine-2-(rs)-carboxamide

HRID 609689Notes

Reaction equation

[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[OH:19][NH:20][C:21]([CH:23]1[CH2:28][N:27]([C:29]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[O:30])[CH2:26][CH2:25][N:24]1[S:39]([N:42]1[CH2:47][CH2:46][CH:45]([C:48]2[C:56]3[C:51](=[CH:52][CH:53]=[C:54]([F:57])[CH:55]=3)[N:50](S(CC[Si](C)(C)C)(=O)=O)[CH:49]=2)[CH2:44][CH2:43]1)(=[O:41])=[O:40])=[O:22].C(O)(=O)C>O1CCCC1>[OH:19][NH:20][C:21]([CH:23]1[CH2:28][N:27]([C:29]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[O:30])[CH2:26][CH2:25][N:24]1[S:39]([N:42]1[CH2:47][CH2:46][CH:45]([C:48]2[C:56]3[C:51](=[CH:52][CH:53]=[C:54]([F:57])[CH:55]=3)[NH:50][CH:49]=2)[CH2:44][CH2:43]1)(=[O:41])=[O:40])=[O:22]

Participants

Conditions

Temperature: 45 °C

Procedure

Tetrabutylammonium fluoride (0.194 ml, 1M solution in tetrahydrofuran) was added to a solution of N-hydroxy-4-benzyloxycarbonyl-1-{4-[5-fluoro-1-(2-trimethylsilylethanesulfonyl)-indol-3-yl]-piperidine-1-sulfonyl}piperazine-2-(RS)-carboxamide (0.067 mg, 0.093 mmol), [prepared as described in Step 7 above] in tetrahydrofuran (1.6 ml). The reaction mixture was heated at 45° C. for approx. 20 min., and then quenched with glacial acetic acid (0.011 ml, 0.194 mmol). The reaction mixture was concentrated and the residue was chromatographed by preparatory TLC (10% methanol/methylene chloride) to give N-hydroxy-4-benzyloxycarbonyl-1-{4-[5-fluoroindol-3-yl]piperidine-1-sulfonyl}piperazine-2-(RS)-carboxamide (71%), mp 85.7-89.7° C.

Workup

concentrationThe reaction mixture was concentrated
customthe residue was chromatographed by preparatory TLC (10% methanol/methylene chloride)

Sources & evidence

ORD record: ord-ee64f3009ac848ed93a359745b7f18a9
Source dataset: uspto-grants-1999_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05998412

Reaction notes

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