Triethylamine → (2R,3S,5S)-5-Formyl-3-isopropyl-2-[4-methoxy-3-(3 methoxy-propoxy)-phenyl]pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 500007Notes

Reaction equation

HRID 500007 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][OH:14])[CH2:11][C@@H:10]([CH:15]([CH3:17])[CH3:16])[C@@H:9]1[C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([O:26][CH2:27][CH2:28][CH2:29][O:30][CH3:31])[CH:19]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C>C(Cl)Cl.CS(C)=O>[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH:13]=[O:14])[CH2:11][C@@H:10]([CH:15]([CH3:17])[CH3:16])[C@@H:9]1[C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([O:26][CH2:27][CH2:28][CH2:29][O:30][CH3:31])[CH:19]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 8471TriethylamineHCID 11998746(2R,3S,5S)-5-Hydroxymethyl-3-isopropyl-2-[4-methoxy-3-(3-methoxy-propoxy)phenyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 11998864(2R,3S,5S)-5-Formyl-3-isopropyl-2-[4-methoxy-3-(3 methoxy-propoxy)-phenyl]pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Using SO3/pyridine complex: A solution of 4.7 g of alcohol 6 in 58 ml of methylene chloride is treated with 33 mL of dimethylsulphoxide and 5.67 g of triethylamine is added. The mixture is cooled to 0° C. and a solution of 6.84 g of the SO3/pyridine complex dissolved in 46 mL of dimethyl sulphoxide is added dropwise within 20 minutes. The reaction is stirred at 0° C. for 2 hours and quenched with 105 mL of water and 105 mL of heptane. The organic layer is separated and washed with 25 mL of 10% aqueous sodium hydrogen sulphate solution. The organic phase is then washed with 110 mL of water followed by 25 mL of saturated aqueous sodium hydrogen carbonate solution. Finally the organic phase is washed with water until the pH of the aqueous solution is 7. The solvent is then removed to give the aldehyde 7 as an oil. A negative [a]d is found at c=1, CHCl3. 1H-NMR (d6-DMSO, 300K) 9.75 (1H), 6.90-6.80 (3H), 4.63-4.30 (3H), 4.00 (2H), 3.75 (3H), 3.50 (3H), 3.23 (3H), 2.10-1.90 (4H), 1.85 (1H), 1.60 (1H), 1.05 (9H), 0.85 (6H).

Workup

  1. additionis added
  2. additionis added dropwise within 20 minutes
  3. customquenched with 105 mL of water and 105 mL of heptane
  4. customThe organic layer is separated
  5. washwashed with 25 mL of 10% aqueous sodium hydrogen sulphate solution
  6. washThe organic phase is then washed with 110 mL of water
  7. washFinally the organic phase is washed with water until the pH of the aqueous solution
  8. customThe solvent is then removed

Sources & evidence

ORD record
ord-fd8834771d3d44aa8d7f32dfc3660983
Source dataset
uspto-grants-2010_08
Patent number
US07767831B2

Reaction notes

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