(3S,6S,8aS)-3-[3-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-3-oxo-propyl]-6-methyl-5-oxo-hexahydro-oxazolo[3,2-a]pyrazine-7-carboxylic acid benzyl ester → (3S,6S,8aR)-3-[3-((S)-4-Hydroxy-6-aza-spiro[2.5]oct-6-yl)-3-oxo-propyl]-6-methyl-5-oxo-hexahydro-oxazolo[3,2-a]pyrazine-7-carboxylic acid benzyl ester

HRID 1261844Notes

Reaction equation

HRID 1261844 reaction equation
COC(=O)[C@@H](N(C(OCC1C=CC=CC=1)=O)CC=O)C.N[C@H](CO)CCC(N1CCC2(CC2)[C@H](O)C1)=O.[CH2:38]([O:45][C:46]([N:48]1[C@@H:53]([CH3:54])[C:52](=[O:55])[N:51]2[C@@H:56]([CH2:59][CH2:60][C:61]([N:63]3[CH2:70][CH2:69][C:66]4([CH2:68][CH2:67]4)[C@H:65]([OH:71])[CH2:64]3)=[O:62])[CH2:57][O:58][C@H:50]2[CH2:49]1)=[O:47])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>>[CH2:38]([O:45][C:46]([N:48]1[C@@H:53]([CH3:54])[C:52](=[O:55])[N:51]2[C@@H:56]([CH2:59][CH2:60][C:61]([N:63]3[CH2:70][CH2:69][C:66]4([CH2:67][CH2:68]4)[C@H:65]([OH:71])[CH2:64]3)=[O:62])[CH2:57][O:58][C@@H:50]2[CH2:49]1)=[O:47])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1

Participants

4

Reactant 3

HCID 67092672(3S,6S,8aS)-3-[3-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-3-oxo-propyl]-6-methyl-5-oxo-hexahydro-oxazolo[3,2-a]pyrazine-7-carboxylic acid benzyl esterHCID 67092882(S)-4-amino-5-hydroxy-1-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-pentan-1-oneHCID 86638111(S)-2-[Benzyloxycarbonyl-(2-oxo-ethyl)-amino]-propionic acid methyl ester2×

Product 1

HCID 67092668(3S,6S,8aR)-3-[3-((S)-4-Hydroxy-6-aza-spiro[2.5]oct-6-yl)-3-oxo-propyl]-6-methyl-5-oxo-hexahydro-oxazolo[3,2-a]pyrazine-7-carboxylic acid benzyl ester

Procedure

Condensation of (S)-2-[benzyloxycarbonyl-(2-oxo-ethyl)-amino]-propionic acid methyl ester (intermediate 1) with (S)-4-amino-5-hydroxy-1-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-pentan-1-one in analogy with examples 1/2F produced a nearly statistical mixture of the title compound [light brown gum, MS: 472.4 (M+H)+], and its epimer, (3S,6S,8aS)-3-[3-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-3-oxo-propyl]-6-methyl-5-oxo-hexahydro-oxazolo[3,2-a]pyrazine-7-carboxylic acid benzyl ester [light brown gum, MS: 472.4 (M+H)|], which were separated by column chromatography (SiO2; DCM→DCM/MeOH/25% aq. ammonia solution 90:10:0.25).

Workup

  1. customproduced

Sources & evidence

ORD record
ord-dca4710ae64f471abfd9c8d6f62fabbd
Source dataset
uspto-grants-2013_06
Patent number
US08471004B2

Reaction notes

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