Water → HCID 59464042, compound

HRID 1713824Notes

Reaction equation

HRID 1713824 reaction equation
[H-].[Na+].C[C:4](P(OC)(O)=O)([C:6]([O-:8])=[O:7])[CH3:5].O=C1[CH2:20][CH2:19][CH:18]([C:21]2[N:26]=[CH:25][C:24]([NH:27][C:28](=[O:37])[O:29][CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[CH:23][CH:22]=2)[CH2:17][CH2:16]1.O.[CH2:39]1COCC1>>[CH2:30]([O:29][C:28]([NH:27][C:24]1[CH:23]=[CH:22][C:21]([CH:18]2[CH2:19][CH2:20][C:5](=[CH:4][C:6]([O:8][CH3:39])=[O:7])[CH2:16][CH2:17]2)=[N:26][CH:25]=1)=[O:37])[C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1

Participants

6

Reactant 5

HCID 962WaterHCID 8028Tetrahydrofuran2×HCID 24758Sodium hydrideHCID 53413272TrimethylphosphonoacetateHCID 59464032HCID 59464032, compound

Product 1

HCID 59464042HCID 59464042, compoundYield 66.7%

Procedure

To an ice water cooled suspension of a 60% mineral oil dispersion of sodium hydride (585 mg, 24.35 mmol) in anhydrous THF (60 mL) was added trimethylphosphonoaceate (3.1 mL, 18.73 mmol). After 10 minutes a solution of benzyl [6-(4-oxocyclohexyl)pyridin-3-yl]carbamate, prepared as above, (4.05 g, 12.49 mmol) in THF (40 mL) was added and the reaction mixture allowed to warm to ambient temperature over the weekend. Water (100 mL) was added and the volatile material was removed under reduced pressure and the mixture extracted into EtOAc (4×200 mL) the organic extracts were combined, washed with brine (50 mL), dried (MgSO4) and concentrated under reduced pressure to leave crude product. This was purified on a 120 g silica SiliCycle cartridge, loading in and eluting 30-50% EtOAc/isohexane to provide the title compound (3.17 g, 66.7%); 1H NMR (CDCl3) δ 1.63-1.76 (m, 2H), 2.03-2.15 (m, 3H), 2.31-2.44 (m, 2H), 2.92-2.97 (m, 1H), 3.69 (s, 3H), 3.92-3.96 (m, 1H), 5.21 (s, 2H), 5.68 (s, 1H), 6.71 (s, 1H), 7.12 (d, 1H), 7.35-7.40 (m, 5H), 8.37 (s, 1H), 8.37 (s, 1H); MS m/e MH+ 381.

Workup

  1. additionwas added
  2. customthe volatile material was removed under reduced pressure
  3. extractionthe mixture extracted into EtOAc (4×200 mL) the organic extracts
  4. washwashed with brine (50 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated under reduced pressure
  7. customto leave crude product
  8. customThis was purified on a 120 g silica SiliCycle cartridge, loading in and
  9. washeluting 30-50% EtOAc/isohexane

Sources & evidence

ORD record
ord-dc263a84c80a48329df703d4231c8d79
Source dataset
uspto-grants-2010_09
Patent number
US07795283B2

Reaction notes

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