3-Hydroxypyridine → (S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-N-((1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((2R,4R)-4-(pyridin-3-yloxy)pyrrolidin-2-yl)propan-2-yl)-4-phenylbutanamide

HRID 132961Notes

Reaction equation

HRID 132961 reaction equation
[C:1]([NH:4][C@:5]1([C@@H:54]([CH2:56][CH3:57])[CH3:55])[CH2:9][CH2:8][N:7]([C@@H:10]([CH2:45][CH2:46][C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[C:11]([NH:13][C@@H:14]([CH2:36][C:37]2[CH:42]=[C:41]([F:43])[CH:40]=[C:39]([F:44])[CH:38]=2)[C@@H:15]([C@H:17]2C[CH2:21][CH2:20][CH2:19][N:18]2C(C2C=CC=CC=2)C2C=CC=CC=2)[OH:16])=[O:12])[C:6]1=[O:53])(=[O:3])[CH3:2].FC1C=C(C=C(F)C=1)C[C@H]1[C@@H]([C@H]2C[C@@H]([O:73][C:74]3[CH:75]=[N:76][CH:77]=[CH:78][CH:79]=3)CN2C(C2C=CC=CC=2)C2C=CC=CC=2)OC(=O)N1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O.FC1C=C(C=C(F)C=1)C[C@H]1[C@@H]([C@H]2C[C@H](O)CN2C(C2C=CC=CC=2)C2C=CC=CC=2)OC(=O)N1.OC1C=NC=CC=1>C1COCC1>[C:1]([NH:4][C@:5]1([C@@H:54]([CH2:56][CH3:57])[CH3:55])[CH2:9][CH2:8][N:7]([C@@H:10]([CH2:45][CH2:46][C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=2)[C:11]([NH:13][C@@H:14]([CH2:36][C:37]2[CH:38]=[C:39]([F:44])[CH:40]=[C:41]([F:43])[CH:42]=2)[C@H:15]([OH:16])[C@H:17]2[CH2:21][C@@H:20]([O:73][C:74]3[CH:75]=[N:76][CH:77]=[CH:78][CH:79]=3)[CH2:19][NH:18]2)=[O:12])[C:6]1=[O:53])(=[O:3])[CH3:2]

Participants

8

Reactant 6

HCID 79713-HydroxypyridineHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 58608198(4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4S)-1-benzhydryl-4-hydroxypyrrolidin-2-yl)oxazolidin-2-oneHCID 69194179(S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-N-((1S,2S)-1-((R)-1-benzhydrylpiperidin-2-yl)-3-(3,5-difluorophenyl)-1-hydroxypropan-2-yl)-4-phenylbutanamideHCID 69195967(4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4R)-1-benzhydryl-4-(pyridin-3-yloxy)pyrrolidin-2-yl)oxazolidin-2-one

Product 1

HCID 69195175(S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-N-((1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((2R,4R)-4-(pyridin-3-yloxy)pyrrolidin-2-yl)propan-2-yl)-4-phenylbutanamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Step 13 (A): (4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4R)-1-benzhydryl-4-(pyridin-3-yloxy)pyrrolidin-2-yl)oxazolidin-2-one. To a solution of triphenylphosphine (54 mg, 0.206 mmol) in THF (2.5 mL) at rt was added DEAD (0.0324 mL, 0.206 mmol). After 1 min, a solution of (4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4S)-1-benzhydryl-4-hydroxypyrrolidin-2-yl)oxazolidin-2-one (Preparation K, 80 mg, 0.172 mmol) in THF (2.5 mL) was added. After 2 min, 3-hydroxypyridine (16.4 mg, 0.172 mmol) was added and the mixture was stirred at rt for 3.5 h. pH 7 buffer was added and the mixture was extracted with ethyl acetate. The combined organic phases were washed with sat. aqueous NaCl, dried (MgSO4), and concentrated in vacuo. Flash chromatography (silica gel, 0-100% ethyl acetate/hexane) gave the title compound: HPLC retention time: 1.39 min (method A). MS (ESI) (M+H)+ 542.18.

Workup

  1. waitAfter 2 min
  2. additionbuffer was added
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe combined organic phases were washed with sat. aqueous NaCl
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c7907e5fd5fe4c9482eb2be183792fd5
Source dataset
uspto-grants-2008_06
Patent number
US07388007B2

Reaction notes

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