(S)-6-((S)-3-amino-4-hydroxy-butyl)-6-aza-spiro[2.5]octan-4-ol → (3S,6S)-3-[2-((S)-4-Hydroxy-6-aza-spiro[2.5]oct-6-yl)-ethyl]-6-methyl-5-oxo-hexahydro-oxazolo[3,2-a]pyrazine-7-carboxylic acid benzyl ester

HRID 1261838Notes

Reaction equation

HRID 1261838 reaction equation
CO[C:3](=[O:20])[C@@H:4]([N:6]([C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])[CH2:7][CH:8]=[O:9])[CH3:5].[NH2:21][C@H:22]([CH2:34]O)[CH2:23][CH2:24][N:25]1[CH2:32][CH2:31][C:28]2([CH2:30][CH2:29]2)[C@H:27]([OH:33])[CH2:26]1>C1(C)C=CC=CC=1>[CH2:13]([O:12][C:10]([N:6]1[C@@H:4]([CH3:5])[C:3](=[O:20])[N:21]2[C@@H:22]([CH2:23][CH2:24][N:25]3[CH2:32][CH2:31][C:28]4([CH2:29][CH2:30]4)[C@H:27]([OH:33])[CH2:26]3)[CH2:34][O:9][CH:8]2[CH2:7]1)=[O:11])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

4

Reactant 2

HCID 67080071(S)-6-((S)-3-amino-4-hydroxy-butyl)-6-aza-spiro[2.5]octan-4-olHCID 86638111(S)-2-[Benzyloxycarbonyl-(2-oxo-ethyl)-amino]-propionic acid methyl ester2×

Product 1

HCID 67092709(3S,6S)-3-[2-((S)-4-Hydroxy-6-aza-spiro[2.5]oct-6-yl)-ethyl]-6-methyl-5-oxo-hexahydro-oxazolo[3,2-a]pyrazine-7-carboxylic acid benzyl esterYield 84.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of (S)-2-[benzyloxycarbonyl-(2-oxo-ethyl)-amino]-propionic acid methyl ester (intermediate 1; 570 mg, 2.04 mmol) and (S)-6-((S)-3-amino-4-hydroxy-butyl)-6-aza-spiro[2.5]octan-4-ol (445 mg, 2.04 mmol) in toluene (6 mL) was heated at reflux for 16 h, then the reaction mixture was concentrated. Chromatography (SiO2; DCM→DCM/MeOH/25% aq. ammonia solution 90:10:0.25) produced the title compound (763 mg, 84%) as a 70:30 mixture of (R)- and (S)-epimers. White foam, MS (ISP)=446.2 (M+H)+.

Workup

  1. temperatureat reflux for 16 h
  2. concentrationthe reaction mixture was concentrated

Sources & evidence

ORD record
ord-4e45a1e0cd914be3816da81850b6319c
Source dataset
uspto-grants-2013_06
Patent number
US08471004B2

Reaction notes

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