HCID 66774307, compound → HCID 66688039, compound

HRID 1644820Notes

Reaction equation

HRID 1644820 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C:9]1([CH2:16][CH:17]1[CH2:19][CH2:18]1)[C:13](O)=[O:14])=[O:7])([CH3:4])([CH3:3])[CH3:2]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C:9]1([CH2:16][CH:17]1[CH2:18][CH2:19]1)[CH2:13][OH:14])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

3

Reactant 1

HCID 66774307HCID 66774307, compound

Product 1

HCID 66688039HCID 66688039, compoundYield 97.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-cyclopropylmethyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (4 g, see example 64 and 65) in THF (100 mL) was added borane-methylsulfide complex (8.9 mL of a 2M solution in THF) dropwise via syringe. The reaction mixture was heated for 4 hours to 80° C. and was then cooled to RT. The THF was removed in vacuo and the residue was then diluted with water and DCM. The phases were separated and the aqueous phase was extracted with further DCM (2×50 mL). The combined organic layers were washed with saturated aqueous sodium bicarbonate solution, brine and dried over sodium sulfate. Filtration of the drying agent and evaporation in vacuo to dryness afforded the crude 2-cyclopropylmethyl-2-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (3.7 g) to which was added Dess-Martin periodinane solution (32.6 mL of a 15% solution in DCM, CAS [87413-09-0]) and the reaction mixture was stirred for 5 hours at RT. The reaction was quenched with 10 mL of saturated aqueous sodium thiosulfate solution and stirred for a further 20 minutes. The phases were separated and the DCM layer was washed with saturate aqueous sodium bicarbonate solution. The aqueous layers were back extracted with further DCM and the combined DCM layers were dried over sodium sulfate, filtered and reduced to dryness in vacuo to afford the desired 2-cyclopropylmethyl-2-formyl-pyrrolidine-1-carboxylic acid tert-butyl ester (2.59 g, MS (ES+): 254.3 (M+H), as a brown oil).

Workup

  1. temperatureThe reaction mixture was heated for 4 hours to 80° C.
  2. customThe THF was removed in vacuo
  3. additionthe residue was then diluted with water and DCM
  4. customThe phases were separated
  5. extractionthe aqueous phase was extracted with further DCM (2×50 mL)
  6. washThe combined organic layers were washed with saturated aqueous sodium bicarbonate solution, brine
  7. dry with materialdried over sodium sulfate
  8. filtrationFiltration of the drying agent and evaporation in vacuo to dryness

Sources & evidence

ORD record
ord-fa133b1fd0aa438bbe87400025d2220a
Source dataset
uspto-grants-2012_02
Patent number
US08124636B2

Reaction notes

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