Hydrochloric Acid → HCID 89921997, compound

HRID 527743Notes

Reaction equation

[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:14][C@@H:13]([OH:15])[CH2:12][C@H:11]1[C:16]([OH:18])=[O:17])=[O:9])([CH3:6])([CH3:5])[CH3:4].Br[CH2:20][C:21]1[CH:30]=[CH:29][C:24]([C:25]([O:27][CH3:28])=[O:26])=[CH:23][CH:22]=1.Cl>CN(C=O)C.C(OCC)(=O)C>[C:3]([O:7][C:8]([N:10]1[CH2:14][C@@H:13]([O:15][CH2:20][C:21]2[CH:22]=[CH:23][C:24]([C:25]([O:27][CH3:28])=[O:26])=[CH:29][CH:30]=2)[CH2:12][C@H:11]1[C:16]([OH:18])=[O:17])=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

Conditions

Temperature: 0 °C

Procedure

Sodium hydride (0.97 g, 24 mmol) was suspended in DMF (15 mL) under nitrogen at 0° C. A solution of (2S,4S)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid (2.0 g, 8.7 mmol) in DMF (20 mL) was added dropwise. The reaction mixture was stirred at 0° C. for 10 min and treated with a solution of methyl 4-(bromomethyl)benzoate (2.3 g, 10 mmol) in DMF (5 mL). The reaction mixture was stirred at 0° C. for 1 h, and mixed with ethyl acetate and 1N HCl solution. The EtOAc layer was separated, washed with brine, and dried over MgSO4. The filtrate was concentrated in vacuo and the residue was purified by flash chromatography (eluting with 20% EtOAc/DCM) to afford the title compound as a white solid (1.2 g, 37%). 1H NMR (CDCl3) δ 7.99 (d, J=8.1 Hz, 2H), 7.36 (d, J=3.5 Hz, 2H), 4.78-4.26 (m, 3H), 4.19-4.11 (m, 1H), 3.90 (s, 3H), 3.71-3.46 (m, 2H), 2.84-2.39 (m, 1H), 2.23-2.04 (m, 1H), 1.48 (br. s., 9H); MS(ESI+) m/z 324.0 (M-55)+.

Workup

stirringThe reaction mixture was stirred at 0° C. for 1 h
customThe EtOAc layer was separated
washwashed with brine
dry with materialdried over MgSO4
concentrationThe filtrate was concentrated in vacuo
customthe residue was purified by flash chromatography (eluting with 20% EtOAc/DCM)

Sources & evidence

ORD record: ord-96495eaba0f0461680c2fcded34e672c
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09345740B2

Reaction notes

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