Water → 3-Carbamoylisoxazol-5-ylmethyl (-)-(R)-3-(naphth-2-yloxymethyl)pyrrolidine-1-carboxylate

HRID 1466003Notes

Reaction equation

HRID 1466003 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[O:11][CH2:12][C@@H:13]1[CH2:17][CH2:16][NH:15][CH2:14]1.[C:18](=O)([O:29]C1C=CC([N+]([O-])=O)=CC=1)[O:19][CH2:20][C:21]1[O:25][N:24]=[C:23]([C:26](=[O:28])[NH2:27])[CH:22]=1.CN1CCOCC1.O>ClCCl>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[O:11][CH2:12][C@@H:13]1[CH2:17][CH2:16][N:15]([C:18]([O:19][CH2:20][C:21]2[O:25][N:24]=[C:23]([C:26](=[O:28])[NH2:27])[CH:22]=2)=[O:29])[CH2:14]1

Participants

6

Reactant 4

HCID 962WaterHCID 79724-MethylmorpholineHCID 26192527(R)-3-(naphth-2-yloxymethyl)pyrrolidineHCID 666608603-Carbamoylisoxazol-5-ylmethyl 4-nitrophenyl carbonate

Product 1

HCID 673509143-Carbamoylisoxazol-5-ylmethyl (-)-(R)-3-(naphth-2-yloxymethyl)pyrrolidine-1-carboxylateYield 38.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

0.21 g (0.92 mmol) of (R)-3-(naphth-2-yloxymethyl)-pyrrolidine is dissolved in 3.80 ml of dichloromethane and then 0.31 g (1.01 mmol) of 3-carbamoylisoxazol-5-ylmethyl 4-nitrophenyl carbonate and 0.15 ml (1.38 mmol) of N-methylmorpholine are added. The mixture is stirred at ambient temperature for 20 hours and then water is added to the reaction medium. After extraction of the aqueous phase with dichloromethane, the organic phases are successively washed three times with a 1M aqueous sodium hydroxide solution and then twice with a saturated aqueous ammonium chloride solution. After having dried the organic phases over sodium sulphate, they are filtered and the filtrate is evaporated to dryness. 0.14 g of the desired product is thus obtained in the form of a white solid after purification on a column of silica gel, elution being carried out with a dichloromethane/methanol mixture, and then taken up in isopropyl ether.

Workup

  1. extractionAfter extraction of the aqueous phase with dichloromethane
  2. washthe organic phases are successively washed three times with a 1M aqueous sodium hydroxide solution
  3. dry with materialAfter having dried the organic phases over sodium sulphate, they
  4. filtrationare filtered
  5. customthe filtrate is evaporated to dryness

Sources & evidence

ORD record
ord-a9c4d1cdfe134fa2be194f04004afc87
Source dataset
uspto-grants-2015_04
Patent number
US09000010B2

Reaction notes

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