Hydrochloric Acid → HCID 67074996, compound

HRID 2095602Notes

Reaction equation

[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH:15]([C:17](=[O:19])[NH2:18])[N:14]([CH2:20][CH2:21][CH2:22][C:23](OC(C)(C)C)=[O:24])[C:13](=[O:30])[C@@H:12]1[CH3:31])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.Cl.[CH2:34]1[C:36]2([CH2:41][CH2:40][NH:39][CH2:38][C@H:37]2[OH:42])[CH2:35]1>>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][C@H:15]([C:17](=[O:19])[NH2:18])[N:14]([CH2:20][CH2:21][CH2:22][C:23]([N:39]2[CH2:40][CH2:41][C:36]3([CH2:34][CH2:35]3)[C@H:37]([OH:42])[CH2:38]2)=[O:24])[C:13](=[O:30])[C@@H:12]1[CH3:31])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Reactant 3

HCID 313Hydrochloric Acid

HCID 44541812(4S)-6-Azaspiro[2.5]octan-4-ol hydrochloride2×

HCID 67087043HCID 67087043, compound

Product 1

HCID 67074996HCID 67074996, compoundYield 22%

Procedure

In analogy to the procedure described in example 120 step D, (2S,5RS)-4-(3-tert-butoxycarbonyl-propyl)-5-carbamoyl-2-methyl-3-oxo-piperazine-1-carboxylic acid benzyl ester was first hydrolysed with HCl and then coupled with (S)-6-aza-spiro[2.5]octan-4-ol hydrochloride (intermediate 2). The two diasterioisomers could be separated by flash column chromatography (SiO2, EtOAc/MeOH 1:0-9:1) affording first (2S,5R)-5-carbamoyl-4-[4-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-4-oxo-butyl]-2-methyl-3-oxo-piperazine-1-carboxylic acid benzyl ester in 22% yield as an amorphous white solid, MS: 487.30 (MH+) and then (2S,5S)-5-carbamoyl-4-[4-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-4-oxo-butyl]-2-methyl-3-oxo-piperazine-1-carboxylic acid benzyl ester in 20% yield as a colorless foam MS: 487.30 (MH+).

Workup

customThe two diasterioisomers could be separated by flash column chromatography (SiO2, EtOAc/MeOH 1:0-9:1)

Sources & evidence

ORD record: ord-5805ae1f0dee4cc486611d73e1aec244
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08445674B2

Reaction notes

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