2,2-Dimethoxypropane → (S)-tert-Butyl 4-((R)-2-(hydroxymethyl)pent-4-en-1-yl)-2,2-dimethyloxazolidine-3-carboxylate

HRID 451822Notes

Reaction equation

[OH:1][CH2:2][C@@H:3]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH2:4][C@H:5]([CH2:9][OH:10])[CH2:6][CH:7]=[CH2:8].B(F)(F)F.CCOCC.CO[C:30](OC)([CH3:32])[CH3:31]>CC(C)=O>[OH:10][CH2:9][C@H:5]([CH2:6][CH:7]=[CH2:8])[CH2:4][C@H:3]1[CH2:2][O:1][C:30]([CH3:32])([CH3:31])[N:11]1[C:12]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:18]

Participants

Conditions

Temperature: 0 °C

Procedure

tert-butyl (2S,4R)-1-hydroxy-4-(hydroxymethyl)hept-6-en-2-ylcarbamate (6.8 g, 26.2 mmol) was dissolved in acetone (150 mL) followed by the addition of BF3.Et2O (2.62 mmol). The reaction mixture was cooled to 0° C. and 2,2-dimethoxypropane (4.1 g, 39.4 mmol) was added. The resulting mixture was stirred at rt for 1 h, TEA (0.5 mL) was added and stirred for another 5 min before evaporating under reduced pressure. The residue was dissolved in Et2O (300 mL), washed with 1 N HCl (80 mL), sat. aq. NaHCO3 (80 mL), brine (80 mL) successively, and dried, filtered, and concentrated under vacuum to give crude (S)-tert-butyl 4-((R)-2-(hydroxymethyl)pent-4-enyl)-2,2-dimethyloxazolidine-3-carboxylate (7.5 g, 96%). It was used for the next step without further purification. 1H NMR (CD3OD) δ 1.4-1.5 (m, 13H), 1.5-1.6 (d, 6H), 1.6-1.9 (m, 2H), 2.0-2.1 (m, 1H), 3.3-3.5 (m, 2H), 3.6-3.8 (m, 2H), 3.8-3.9 (m, 2H), 4.1-4.2 (m, 1H), 5.0-5.1 (m, 2H), 5.7-5.8 (m, 1H).

Workup

stirringstirred for another 5 min
custombefore evaporating under reduced pressure
dissolutionThe residue was dissolved in Et2O (300 mL)
washwashed with 1 N HCl (80 mL), sat. aq. NaHCO3 (80 mL), brine (80 mL) successively
customdried
filtrationfiltered
concentrationconcentrated under vacuum

Sources & evidence

ORD record: ord-2eba2a6de2474a8e90c1f00c7ede099a
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08487108B2

Reaction notes

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