Barium hydroxide, monohydrate → (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-(5-methoxy-2-(pent-4-enyl)benzylamino)butan-2-ol

HRID 501711

Reaction equation

FC(F)(F)C(O)=O.[F:8][C:9]1[CH:10]=[C:11]([CH2:16][C@H:17]([NH:36]C(=O)OCC2C=CC=CC=2)[C@H:18]([OH:35])[CH2:19][NH:20][CH2:21][C:22]2[CH:27]=[C:26]([O:28][CH3:29])[CH:25]=[CH:24][C:23]=2[CH2:30][CH2:31][CH2:32][CH:33]=[CH2:34])[CH:12]=[C:13]([F:15])[CH:14]=1.O.[OH-].[Ba+2].[OH-]>COCCOC.O>[NH2:36][C@@H:17]([CH2:16][C:11]1[CH:12]=[C:13]([F:15])[CH:14]=[C:9]([F:8])[CH:10]=1)[C@H:18]([OH:35])[CH2:19][NH:20][CH2:21][C:22]1[CH:27]=[C:26]([O:28][CH3:29])[CH:25]=[CH:24][C:23]=1[CH2:30][CH2:31][CH2:32][CH:33]=[CH2:34]

Participants

Conditions

Temperature: 110 °C

Procedure

Step AH (6): To a solution of benzyl (2S,3R)-1-(3,5-difluorophenyl)-3-hydroxy-4-(5-methoxy-2-(pent-4-enyl)benzylamino)butan-2-ylcarbamate trifluoroacetate salt (91.3 mg, 0.140 mmol) in DME (9.0 mL) and water (6.0 mL) was added barium hydroxide monohydrate (831.2 mg, 4.389 mmol). The reaction mixture was stirred at 110° C. in a high-pressure vial for 18 h. The reaction was filtered through a pad of celite and the filtrate was concentrated in vacuum. The residue was purified by silica gel chromatography to give (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-(5-methoxy-2-(pent-4-enyl)benzylamino)butan-2-ol double trifluoroacetate salt (45.8 mg, 52%) as colorless oil. LC-MS (M+H)+=405.42. 1H NMR (CD3OD, 500 MHz) δ 7.30-6.75 (m, 6H) 5.86 (m, 1H) 5.02 (m, 2H) 4.33 (m, 1H) 3.81 (s, 3H) 3.72 (m, 2H) 3.37 (m, 1H) 3.12-2.92 (m, 2H) 2.75-2.60 (m, 2H) 2.14 (m, 2H) 1.65 (m, 2H) 1.53 (m, 2H).

Workup

filtrationThe reaction was filtered through a pad of celite
concentrationthe filtrate was concentrated in vacuum
customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record: ord-f15da352e5b64ec7a47b3ae67c356c99
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07772221B2

Linked notes

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