Acetaldehyde → Tert-butyl 3-(ethylamino)pyrrolidine-1-carboxylate

HRID 1983767Notes

Reaction equation

[NH2:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1.[CH:14](=O)[CH3:15].[BH4-].[Na+]>CO>[C:10]([O:9][C:7]([N:4]1[CH2:5][CH2:6][CH:2]([NH:1][CH2:14][CH3:15])[CH2:3]1)=[O:8])([CH3:13])([CH3:12])[CH3:11]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of (R)-3-amino-1-N-Boc pyrrolidine (1 eq, 5.37 mmol) in methanol (20 mL) was added acetaldehyde (0.95 eq) and the resulting mixture was heated to 80° C. and stirred for 2 h., then stirred at room temperature overnight. Sodium borohydride (0.95 eq, 5.1 mmol ) was added and reaction mixture was stirred for an additional 2 h. The reaction mixture was concentrated, dissolved in ethyl acetate and washed with saturated aqueous sodium bicarbonate. The combined organics were washed with brine and dried over sodium sulfate. The crude product was purified on silica using hexane/ethyl acetate (10%) to hexane/ethyl acetate (50%). 1H-NMR (CDCL3) δ: 1.05 (3H, t), 1.45 (9H, s), 1.60-1.75 (1H, m), 2.00-2.10 (1H, m), 2.68 (4H, q), 2.90-3.15 (1H, m), 3.25-3.65 (4H, m). ESI-MS m/z: 215 (M+1), UV retention time: 0.75 min.

Workup

stirringstirred at room temperature overnight
customreaction mixture
stirringwas stirred for an additional 2 h
concentrationThe reaction mixture was concentrated
dissolutiondissolved in ethyl acetate
washwashed with saturated aqueous sodium bicarbonate
washThe combined organics were washed with brine
dry with materialdried over sodium sulfate
customThe crude product was purified on silica

Sources & evidence

ORD record: ord-eae6c270c5f14fe482c420cde9e6fc5e
Source dataset: uspto-grants-2009_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07541365B2

Reaction notes

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