Tributylphosphine → HCID 54246547, compound

HRID 1582365Notes

Reaction equation

HRID 1582365 reaction equation
N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[C:19]([O:23][C:24]([NH:26][C:27]1[CH:31]=[N:30][S:29][N:28]=1)=[O:25])([CH3:22])([CH3:21])[CH3:20].[CH2:32]([N:39]1[CH2:44][CH2:43][C:42]([C:45]2[C:50]([F:51])=[CH:49][C:48]([N:52]3[CH2:56][C@H:55]([CH2:57]O)[O:54][C:53]3=[O:59])=[CH:47][C:46]=2[F:60])=[CH:41][CH2:40]1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C(P(CCCC)CCCC)CCC>O1CCCC1>[CH2:32]([N:39]1[CH2:44][CH2:43][C:42]([C:45]2[C:50]([F:51])=[CH:49][C:48]([N:52]3[CH2:56][C@H:55]([CH2:57][N:26]([C:27]4[CH:31]=[N:30][S:29][N:28]=4)[C:24]([O:23][C:19]([CH3:22])([CH3:20])[CH3:21])=[O:25])[O:54][C:53]3=[O:59])=[CH:47][C:46]=2[F:60])=[CH:41][CH2:40]1)[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 11304129(5R)-3-(4-(1-benzyl-1,2,5,6-tetrahydropyridin-4-yl)-3,5-difluorophenyl)-5-hydroxymethyloxazolidin-2-oneHCID 22719942152513-86-5

Product 1

HCID 54246547HCID 54246547, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1,1′-(Azodicarbonyl)dipiperidine (680 mg, 2.7 mM) was added portionwise to a stirred solution of 3-t-butyloxycarbonylamino-1,2,5-thiadiazole (543 mg, 2.7 mM, see WO 93-13091), 3-(4-(1-benzyl-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)-5(R)-hydroxymethyloxazolidin-2-one (720 mg, 1.8 mM; prepared by analogy with 3-fluoro compound—see WO 97-30995) and tributylphosphine (540 mg, 2.7 mM) in dry tetrahydrofuran (25 ml) at 0° under nitrogen. The mixture was stirred at 0° for 30 minutes and then at ambient temperature for 3 hours. The mixture was filtered and the filtrate evaporated. The residue was purified, firstly on a silica Mega Bond Elut® column, eluting with a gradient increasing in polarity from 0 to 30% ethyl acetate in isohexane and then on an Isolute SCX ion exchange column, washing with a gradient increasing, in polarity from 0 to 10% methanol in dichloromethane and then eluting with dichloromethane/methanol/0.88SG ammonia 87:10:3 to give the title product as a solid (669 mg, 64% ). NMR (DMSO-d6) δ: 1.49 (s, 9H); 2.30 (brs, 2H); 2.61 (t, 2H); 3.04 (m, 2H); 3.58 (s, 2H); 3.88 (dd, 1H); 4.13 (dd, 1H); 4.20 (dd, 1 H); 4.35 (dd, 1H); 5.02 (m, 1H); 5.79 (brs, 1H); 7.20-7.33 (m, 7H); 8.96 (s, 1H). MS (ESP): 584 (MH+) for C29H31F2N5O4S

Workup

  1. waitat ambient temperature for 3 hours
  2. filtrationThe mixture was filtered
  3. customthe filtrate evaporated
  4. customThe residue was purified, firstly on a silica Mega Bond Elut® column
  5. washeluting with
  6. temperaturea gradient increasing in polarity from 0 to 30% ethyl acetate in isohexane
  7. washon an Isolute SCX ion exchange column, washing with a gradient
  8. temperatureincreasing, in polarity from 0 to 10% methanol in dichloromethane
  9. washeluting with dichloromethane/methanol/0.88SG ammonia 87:10:3

Sources & evidence

ORD record
ord-79080d22356b400ea96bb1f9336af841
Source dataset
uspto-grants-2004_05
Patent number
US06734200B1

Reaction notes

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