3-(TrifluoroMethoxy)phenyl isocyanate → (4S)-6-Azaspiro[2.5]octan-4-ol hydrochloride

HRID 2095599Notes

Reaction equation

HRID 2095599 reaction equation
N(C1C=CC=C(OC(F)(F)F)C=1)=C=O.[Cl:15][C:16]1[CH:17]=[C:18]([N:26]2[CH2:31][CH2:30][N:29]([C@H:32]([CH2:38][O:39][CH3:40])[CH2:33][CH2:34][C:35](O)=[O:36])[C:28](=[O:41])[C@@H:27]2[CH3:42])[CH:19]=[CH:20][C:21]=1[C:22]([F:25])([F:24])[F:23].[CH2:43]1[C:45]2([CH2:50][CH2:49][NH:48][CH2:47][C@H:46]2[OH:51])[CH2:44]1>CCCCCCC.C(O)(C)C>[ClH:15].[CH2:21]1[C:20]2([CH2:19][CH2:18][NH:26][CH2:27][C@H:28]2[OH:41])[CH2:22]1.[Cl:15][C:16]1[CH:17]=[C:18]([N:26]2[CH2:31][CH2:30][N:29]([C@H:32]([CH2:38][O:39][CH3:40])[CH2:33][CH2:34][C:35]([N:48]3[CH2:49][CH2:50][C:45]4([CH2:43][CH2:44]4)[C@H:46]([OH:51])[CH2:47]3)=[O:36])[C:28](=[O:41])[C@@H:27]2[CH3:42])[CH:19]=[CH:20][C:21]=1[C:22]([F:24])([F:25])[F:23]

Participants

6

Reactant 3

HCID 200675553-(TrifluoroMethoxy)phenyl isocyanateHCID 44541813(4S)-6-Azaspiro[2.5]octan-4-olHCID 67074561(S)-4-[(S)-4-(3-Chloro-4-trifluoromethyl-phenyl)-3-methyl-2-oxo-piperazin-1-yl]-5-methoxy-pentanoic acid2×

Product 2

HCID 44541812(4S)-6-Azaspiro[2.5]octan-4-ol hydrochlorideHCID 58232129(S)-4-(3-Chloro-4-trifluoromethyl-phenyl)-1-[(S)-4-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-1-methoxymethyl-4-oxo-butyl]-3-methyl-piperazin-2-one

Reagents, catalysts & solvents 1

HCID 21225753Isopropanol heptaneSolvent

Procedure

In analogy to intermediate 15, (S)-4-[(S)-4-(3-chloro-4-trifluoromethyl-phenyl)-3-methyl-2-oxo-piperazin-1-yl]-5-methoxy-pentanoic acid (61% ds) (intermediate 45) and 1.1 eq. of (S)-6-aza-spiro[2.5]octan-4-ol; hydrochloride (intermediate 2) gave after flash chromatography (SiO2, n-heptane/isopropanol 1:1) the titled compound in 30% yield (90% ds) as off-white waxy solid. MS: 532.22 (MH+, 1Cl).

Sources & evidence

ORD record
ord-457f8e9281a445b4bc55ddfb8083d783
Source dataset
uspto-grants-2013_05
Patent number
US08445674B2

Reaction notes

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