(Diethylamino)sulfur trifluoride → HCID 118207321, compound

HRID 1507228Notes

Reaction equation

HRID 1507228 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][C:28]=1[CH3:29])[CH2:5][N:6]1[CH2:10][CH2:9][CH:8]([N:11]2[CH2:16][CH2:15][C@H:14]([C:17]3[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=3)[C@@H:13](O)[CH2:12]2)[C:7]1=[O:25].CCN(S(F)(F)[F:36])CC>C(Cl)Cl.C(=O)(O)[O-]>[F:36][C@@H:13]1[C@@H:14]([C:17]2[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=2)[CH2:15][CH2:16][N:11]([CH:8]2[CH2:9][CH2:10][N:6]([CH2:5][C:4]3[CH:26]=[CH:27][C:28]([CH3:29])=[C:2]([F:1])[CH:3]=3)[C:7]2=[O:25])[CH2:12]1

Participants

5

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 118207579HCID 118207579, compound

Product 1

HCID 118207321HCID 118207321, compoundYield 54.2%

Reagents, catalysts & solvents 2

HCID 769Bicarbonate IonSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-(3-fluoro-4-methylbenzyl)-3-((3R,4R)-3-hydroxy-4-(4-hydroxyphenyl)-piperidin-1-yl)pyrrolidin-2-one (from step F, 1.9 g, 4.8 mmol) in DCM (35 mL) at 0° C. was added DAST (3.2 mL, 23.8 mmol) under nitrogen. The reaction mixture was allowed to warm to rt and stirred for 2 h, and then diluted with saturated bicarbonate solution and extracted with 200 mL of DCM. The organic layer was dried over Na2SO4, filtered, and evaporated under reduced pressure to give a crude product which was purified via preparative HPLC (method J) to yield 3-((3R,4R)-3-fluoro-4-(4-hydroxyphenyl)piperidin-1-yl)-1-(3-fluoro-4-methylbenzyl)pyrrolidin-2-one (1.1 g, 2.6 mmol) as a pair of diastereomers. LCMS (Method F) RT: 2.13 min, m/z 401. (M+H)+.

Workup

  1. extractionextracted with 200 mL of DCM
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. customevaporated under reduced pressure
  5. customto give a crude product which
  6. customwas purified via preparative HPLC (method J)

Sources & evidence

ORD record
ord-0993292bd3424f35bb5862a4f1694256
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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