(2R)-2-(Phenoxymethyl)oxirane → (2R,3R,4S)-3-benzyloxy-4-dibenzylamino-5-(3,5-difluoro-phenyl)-2-((R)-2-hydroxy-3-phenoxypropylamino)-pentan-1-ol

HRID 20376Notes

Reaction equation

[O:1]([CH2:8][C@H:9]1[CH2:11][O:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:12][C@@H:13]([C@@H:16]([O:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[C@@H:17]([N:27]([CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[CH2:18][C:19]1[CH:24]=[C:23]([F:25])[CH:22]=[C:21]([F:26])[CH:20]=1)[CH2:14][OH:15]>C(O)C>[CH2:43]([O:42][C@@H:16]([C@@H:17]([N:27]([CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[CH2:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)[CH2:18][C:19]1[CH:20]=[C:21]([F:26])[CH:22]=[C:23]([F:25])[CH:24]=1)[C@H:13]([NH:12][CH2:11][C@@H:9]([OH:10])[CH2:8][O:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH2:14][OH:15])[C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1

Participants

Conditions

Temperature: 80 °C

Procedure

Add (R)-2-phenoxymethyl-oxirane (0.189 g, 1.258 mmol) to a solution of (2R,3R,4S)-2-amino-3-benzyloxy-4-dibenzylamino-5-(3,5-difluorophenyl)-pentan-1-ol (0.205 g, 0.434 mmol) in ethanol (2.1 mL). Heat in a sealed vessel at 80° C. overnight. Concentrate and purify (silica gel chromatography, eluting with 1-1.5% 2 M ammonia in methanol/dichloromethane) to give the desired compound as a clear semi-solid (0.165 g, 56.9%).

Workup

concentrationConcentrate
custompurify
wash(silica gel chromatography, eluting with 1-1.5% 2 M ammonia in methanol/dichloromethane)

Sources & evidence

ORD record: ord-6753e69a319f47dc8d39b53e137d0496
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07745438B2

Reaction notes

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