Carbon Dioxide → HCID 86673650, compound

HRID 924328Notes

Reaction equation

HRID 924328 reaction equation
[CH:1](NC(C)C)([CH3:3])[CH3:2].[CH2:8]([Li])CCC.N#N.[C:15]1([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH:20]=[CH:19][C:18]([CH2:21][C@H:22]2[N:26]([CH2:27][C:28]3[CH:33]=[CH:32][C:31](OC)=[CH:30][CH:29]=3)[C:25](=[O:36])[CH2:24][CH2:23]2)=[CH:17][CH:16]=1.C(=O)=O.[O:46]1[CH2:50][CH2:49][CH2:48][CH2:47]1>>[C:50]([C@@H:24]1[CH2:23][CH:22]([CH2:21][C:18]2[CH:19]=[CH:20][C:15]([C:37]3[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=3)=[CH:16][CH:17]=2)[N:26](/[CH:27]=[CH:28]/[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:8]=2)[C:25]1=[O:36])(=[O:46])[C:49]1[CH:3]=[CH:1][CH:2]=[CH:47][CH:48]=1

Participants

7

Reactant 6

HCID 280Carbon DioxideHCID 947NitrogenHCID 7912DiisopropylamineHCID 8028Tetrahydrofuran2×HCID 53311905HCID 53311905, compoundHCID 178418339Butyllithium

Product 1

HCID 86673650HCID 86673650, compound

Procedure

To a solution of diisopropyl amine (2.4 g, 24.0 mmol) in 20 mL of anhydrous tetrahydrofuran is added n-butyllithium (8.8 mL, 22.0 mmol, 2.5 M in hexane) dropwise under N2 at −10˜15° C., stir at this temperature for 1 h, add a solution of (S)-2-Biphenyl-4-ylmethyl-5-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (3a, R1=t-butoxycarbonyl) (7.0 g, 20.0 mmol) in 10 mL of anhydrous tetrahydrofuran dropwise, stir for 1 h, introduce CO2 for 1 h, quench with saturated NH4Cl aqueous solution, extract with ethyl acetate, the combined organic phase is washed with brine, dry over anhydrous sodium sulfate, evaporate the solvent under vacuum, the residue is purified by column chromatography to obtain (S)-5-Biphenyl-4-ylmethyl-2-oxo-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester (4a, R1=t-butoxycarbonyl, R4=hydroxyl) 1HNMR (400 MHz, CDCl3): 1.59 (s, 1H, Boc), 1.85 (m, 1H, 3CHH), 2.36 (m, 1H, 3CHH), 2.48 (m, 1H, 5-CH2), 2.83 (m, 1H, 5-CH2), 3.09 (m, 1H, 2-CH), 4.40 (m, 1H, 4-CH), 6.10 (d, 1H, C═CHH), 7.23˜7.56 (9H, m, aromatic). The ratio of (3S,5S) to (3R,5S) is 36:64 as determined by HPLC.

Workup

  1. stirringstir for 1 h
  2. customquench with saturated NH4Cl aqueous solution
  3. extractionextract with ethyl acetate
  4. washthe combined organic phase is washed with brine
  5. dry with materialdry over anhydrous sodium sulfate
  6. customevaporate the solvent under vacuum
  7. customthe residue is purified by column chromatography

Sources & evidence

ORD record
ord-036c58cdb82c43b4bc7c8119877195bb
Source dataset
uspto-grants-2016_03
Patent number
US09278908B2

Reaction notes

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