benzyl (2S,3R)-4-((R)-2-(allyloxy)-1-phenylethylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-ylcarbamate → (2R,3S)-1-((R)-2-(allyloxy)-1-phenylethylamino)-3-amino-4-(3,5-difluorophenyl)butan-2-ol

HRID 501682Notes

Reaction equation

[CH2:1]([O:4][CH2:5][C@H:6]([NH:13][CH2:14][C@@H:15]([OH:37])[C@@H:16]([NH:26]C(=O)OCC1C=CC=CC=1)[CH2:17][C:18]1[CH:23]=[C:22]([F:24])[CH:21]=[C:20]([F:25])[CH:19]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH:2]=[CH2:3]>COCCOC.O>[CH2:1]([O:4][CH2:5][C@H:6]([NH:13][CH2:14][C@@H:15]([OH:37])[C@@H:16]([NH2:26])[CH2:17][C:18]1[CH:19]=[C:20]([F:25])[CH:21]=[C:22]([F:24])[CH:23]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH:2]=[CH2:3]

Participants

Conditions

Temperature: 110 °C

Procedure

Step Q (5): A mixture of benzyl (2S,3R)-4-((R)-2-(allyloxy)-1-phenylethylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-ylcarbamate (1.1 g, 2.15 mmol) from step Q (4), Ba(OH)2.H2O (1.23 g, 6.47 mmol), and DME/H2O (12 mL/8 mL) was heated at 110° C. in a sealed tube. After 18 h, the vessel was cooled to rt and the precipitate was removed by filtration. The vessel and filtercake were rinsed with fresh DME and the combined filtrates were concentrated in vacuo. The crude product was purified by silica gel chromatography to give 550 mg (68% yield) of the title compound as a yellow viscous oil. LC-MS (M+H)+=377.4; 1H NMR (300 MHz, CDCl3) δ ppm 2.46-3.01 (m, 3H) 3.13-3.72 (m, 7H) 3.89-4.04 (m, 2H) 5.10-5.28 (m, 2H) 5.77-5.96 (m, 1H) 6.52-6.78 (m, 3H) 7.24-7.41 (m, 4H).

Workup

temperaturethe vessel was cooled to rt
customthe precipitate was removed by filtration
washThe vessel and filtercake were rinsed with fresh DME
concentrationthe combined filtrates were concentrated in vacuo
customThe crude product was purified by silica gel chromatography

Sources & evidence

ORD record: ord-21e9ea14c1034daea4d27b9f9100b4e1
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07772221B2

Reaction notes

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