1,1-Dichloroethane → (R)-3-(4-benzyloxy-2,6-dichloro-benzyl)-1-(4-hydroxy-piperidin-1-yl)-pyrrolidin-2-one

HRID 1692097Notes

Reaction equation

HRID 1692097 reaction equation
ClC(Cl)C.[NH2:5][N:6]1[CH2:11][CH2:10][CH:9]([OH:12])[CH2:8][CH2:7]1.C([C@@H]1COC(=O)N1[C:26](=[O:48])[C@H:27]([CH2:31][C:32]1[C:37]([Cl:38])=[CH:36][C:35]([O:39][CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)=[CH:34][C:33]=1[Cl:47])[CH2:28][CH:29]=O)C1C=CC=CC=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[CH2:40]([O:39][C:35]1[CH:34]=[C:33]([Cl:47])[C:32]([CH2:31][C@@H:27]2[CH2:28][CH2:29][N:5]([N:6]3[CH2:11][CH2:10][CH:9]([OH:12])[CH2:8][CH2:7]3)[C:26]2=[O:48])=[C:37]([Cl:38])[CH:36]=1)[C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1

Participants

6

Reactant 4

HCID 63651,1-DichloroethaneHCID 5049666Sodium triacetoxyborohydrideHCID 121256451-Aminopiperidin-4-OLHCID 59515429(R)-4-((R)-benzyl-2-oxo-oxazolidin-3-yl)-3-(4-benzyloxy-2,6-dichloro-benzyl)-4-oxo-butyraldehyde

Product 1

HCID 57672050(R)-3-(4-benzyloxy-2,6-dichloro-benzyl)-1-(4-hydroxy-piperidin-1-yl)-pyrrolidin-2-oneYield 90%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Stir a mixture of dichloroethane (500 mL), N-amino-4-hydroxypiperidine (10.66 g, 91.88 mmol), (R)-4-((R)-4-benzyl-2-oxo-oxazolidin-3-yl)-3-(4-benzyloxy-2,6-dichloro-benzyl)-4-oxo-butyraldehyde (40.2 g, 76.57 mmol) and sodium triacetoxyborohydride (48.47 g, 229.71 mmol) at room temperature for 21 hours. Bring the reaction to 55° C. and is stir for 1 hour. Cool the reaction, dilute with dichloromethane, and wash with water. Dry the organic layer (Na2SO4), remove the solvent in vacuo to afford crude product, and purify on silica with a 100% ethyl acetate and 10% methanol in methylene chloride to afford 30 g (90%) of the titled product. MS (m/z): 449 (M+).

Workup

  1. customBring the reaction to 55° C.
  2. stirringis stir for 1 hour
  3. temperatureCool
  4. customthe reaction
  5. washwash with water
  6. dry with materialDry the organic layer (Na2SO4)
  7. customremove the solvent in vacuo
  8. customto afford crude product
  9. custompurify on silica with a 100% ethyl acetate and 10% methanol in methylene chloride

Sources & evidence

ORD record
ord-d2f2051e3b0547eabe33273ce1c0782b
Source dataset
uspto-grants-2012_04
Patent number
US08153807B2

Reaction notes

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