Chlorotrimethylsilane → (2S)-di-tert-butyl 4-(2-ethoxy-2-oxoethyl)-4-hydroxypyrrolidine-1,2-dicarboxylate

HRID 2038553Notes

Reaction equation

HRID 2038553 reaction equation
Cl[Si](C)(C)C.[O:6]=[C:7]1[CH2:11][N:10]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[C@H:9]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:8]1.Br[CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29]>[Zn].C1COCC1>[CH2:31]([O:30][C:28](=[O:29])[CH2:27][C:7]1([OH:6])[CH2:11][N:10]([C:12]([O:14][C:15]([CH3:16])([CH3:17])[CH3:18])=[O:13])[C@H:9]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:8]1)[CH3:32]

Participants

6

Reactant 3

HCID 6397ChlorotrimethylsilaneHCID 7748Ethyl bromoacetateHCID 11346670(S)-di-tert-butyl 4-oxopyrrolidine-1,2-dicarboxylate

Product 1

HCID 59547296(2S)-di-tert-butyl 4-(2-ethoxy-2-oxoethyl)-4-hydroxypyrrolidine-1,2-dicarboxylateYield 73%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalyst2×HCID 8028TetrahydrofuranSolvent2×

Procedure

Zinc dust (1.05 g, 16 mmol, 1.6 eq.) in a flask was heated with a heat gun two times. Dry THF (10 mL) and chlorotrimethylsilane (0.405 mL, 3.2 mmol, 0.32 eq.) were added to this flask. The suspension was stirred for 15 min at room temp., heated to reflux, and then removed from the heat. (S)-di-tert-butyl 4-oxopyrrolidine-1,2-dicarboxylate (2.85 g, 10 mmol, 1 eq.) and ethyl 2-bromoacetate (1.77 mL, 16 mmol, 1.6 eq.) were combined with dry THF (10 mL), and added slowly to the Zinc suspension at a rate that at which a gentle reflux was observed. The reaction was refluxed for 2 hrs and monitored by TLC. Upon completion, the reaction was concentrated. Chromatography using hexanes and ethyl acetate gave 2.64 g (7.3 mmol) of (2S)-di-tert-butyl 4-(2-ethoxy-2-oxoethyl)-4-hydroxypyrrolidine-1,2-dicarboxylate (A1) as a 4:1 (2S,4S:2S,4R) mixture of the diastereomers. 1H NMR (300 MHz, DMSO) 4.97 (m, 1H), 4.14-4.01 (m, 3H), 3.48-3.33 (m, 2H), 2.56 (m, 2H), 2.35-2.19 (m, 1H), 2.03 (dd, 1H), 1.40-1.35 (m, 18H), 1.18 (t, 3H).

Workup

  1. temperatureheated
  2. temperatureto reflux
  3. customremoved from the heat
  4. temperaturea gentle reflux
  5. temperatureThe reaction was refluxed for 2 hrs
  6. concentrationUpon completion, the reaction was concentrated

Sources & evidence

ORD record
ord-4bb61310a9834801b0faf1e69cfbd419
Source dataset
uspto-grants-2013_11
Patent number
US08575208B2

Reaction notes

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