N-(3,4-dichlorophenyl)alanine → HCID 59159254, compound

HRID 1096294Notes

Reaction equation

HRID 1096294 reaction equation
C([Si](CC)(CC)O[C@@H](CCN1CCC2(CC2)[C@H](O[Si](CC)(CC)CC)C1)CN)C.COC(OC)CNC[C@@H](O[Si](CC)(CC)CC)CCN1CCC2(CC2)[C@H](O[Si](CC)(CC)CC)C1.ClC1C=C(N[C@@H](C)C(O)=O)C=CC=1Cl.[Cl:79][C:80]1[CH:81]=[C:82]([NH:87][C@@H:88]([CH3:126])[C:89]([N:91]([CH2:120][CH:121](OC)OC)[CH2:92][C@@H:93]([O:112][Si](CC)(CC)CC)[CH2:94][CH2:95][N:96]2[CH2:103][CH2:102][C:99]3([CH2:101][CH2:100]3)[C@H:98]([O:104][Si](CC)(CC)CC)[CH2:97]2)=[O:90])[CH:83]=[CH:84][C:85]=1[Cl:86]>>[Cl:79][C:80]1[CH:81]=[C:82]([N:87]2[CH2:121][CH2:120][N:91]([CH2:92][C@@H:93]([OH:112])[CH2:94][CH2:95][N:96]3[CH2:103][CH2:102][C:99]4([CH2:101][CH2:100]4)[C@H:98]([OH:104])[CH2:97]3)[C:89](=[O:90])[C@@H:88]2[CH3:126])[CH:83]=[CH:84][C:85]=1[Cl:86]

Participants

5

Reactant 4

HCID 5491659N-(3,4-dichlorophenyl)alanine2×HCID 66782849HCID 66782849, compoundHCID 66783483HCID 66783483, compoundHCID 66783604HCID 66783604, compound

Product 1

HCID 59159254HCID 59159254, compound

Procedure

The title compound was produced in analogy with example 104, steps A-H. Thus, reaction of 2-allyl-oxirane with benzyl carbamate in the presence of (1R,2R)-(−)-N—N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediaminocobalt(II) in step A led to ((S)-2-hydroxy-pent-4-enyl)-carbamic acid benzyl ester, which was converted to ((S)-2-hydroxy-4-oxo-butyl)-carbamic acid benzyl ester in step B. This underwent a reductive amination reaction with (S)-6-aza-spiro[2.5]octan-4-ol hydrochloride in step C, leading to [(S)-2-hydroxy-4-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-butyl]-carbamic acid benzyl ester. Silylation in step D gave [(S)-2-triethylsilanyloxy-4-((S)-4-triethylsilanyloxy-6-aza-spiro[2.5]oct-6-yl)-butyl]-carbamic acid benzyl ester, which was hydrogenated to (S)-2-triethylsilanyloxy-4-((S)-4-triethylsilanyloxy-6-aza-spiro[2.5]oct-6-yl)-butylamine in step E. This was converted to (2,2-dimethoxy-ethyl)-[(S)-2-triethylsilanyloxy-4-((S)-4-triethylsilanyloxy-6-aza-spiro[2.5]oct-6-yl)-butyl]-amine in step F, followed by coupling with (S)-2-(3,4-dichloro-phenylamino)-propionic acid (intermediate 24) in step G, leading to (S)-2-(3,4-dichloro-phenylamino)-N-(2,2-dimethoxy-ethyl)-N—[(S)-2-triethylsilanyloxy-4-((S)-4-triethylsilanyloxy-6-aza-spiro[2.5]oct-6-yl)-butyl]-propionamide. Finally, reductive cyclization and concomitant desilylation in step H afforded (S)-4-(3,4-dichloro-phenyl)-1-[(S)-2-hydroxy-4-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-butyl]-3-methyl-piperazin-2-one. Colourless gum, MS: 456.3 (M+H)+.

Sources & evidence

ORD record
ord-5f2ad19cc82440d3a36acf99dbf07097
Source dataset
uspto-grants-2012_03
Patent number
US08138175B2

Reaction notes

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