N,N,N',N'-Tetramethylazodicarboxamide → HCID 69279691, compound

HRID 1767900Notes

Reaction equation

[C:1]([O:5][C:6](=[O:18])[CH2:7][N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([OH:17])[CH:15]=2)[CH:10]=[CH:9]1)([CH3:4])([CH3:3])[CH3:2].[CH3:19][C:20]1[N:21]=[C:22]([C:28]2[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=2)[S:23][C:24]=1[C@H:25](O)[CH3:26].C(P(CCCC)CCCC)CCC.CN(C)C(N=NC(N(C)C)=O)=O>>[C:1]([O:5][C:6](=[O:18])[CH2:7][N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:17][C@H:25]([C:24]3[S:23][C:22]([C:28]4[CH:29]=[CH:30][C:31]([C:34]([F:36])([F:37])[F:35])=[CH:32][CH:33]=4)=[N:21][C:20]=3[CH3:19])[CH3:26])[CH:15]=2)[CH:10]=[CH:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

Reactant 4

HCID 4278N,N,N',N'-Tetramethylazodicarboxamide

HCID 13831Tributylphosphine

HCID 58697769HCID 58697769, compound

HCID 69283069tert-Butyl (6-hydroxy-1H-indol-1-yl)acetate

Product 1

HCID 69279691HCID 69279691, compound

Procedure

In analogy to the procedure described in example 3 c], (6-hydroxy-indol-1-yl)-acetic acid tert-butyl ester (example 6 b]) was reacted with (R)-1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-ethanol [ee=79%; PCT Int. Appl. (2002), WO 02/062774 A1] in the presence of tributylphosphine and N,N,N′,N′-tetramethyl azodicarboxamide to obtain (S)-(6-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-ethoxy}-indol-1-yl)-acetic acid tert-butyl ester as colorless liquid. The configuration was tentatively assigned as S according to R. Cadilla et al., PCT Int. Appl. (2002), WO 02/062774 A1 and the generally accepted SN2-type mechanism of the Mitsunobu reaction.

Sources & evidence

ORD record: ord-7a50b0e057b940c2ab8a489079e88cc1
Source dataset: uspto-grants-2007_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07235572B2

Reaction notes

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