1,8-Diazabicyclo(5.4.0)undec-7-ene → (E)-ethyl 2-fluoro-3-(N-Boc-piperdin-4-yl)propenoate

HRID 380591Notes

Reaction equation

HRID 380591 reaction equation
[Cl-].[Li+].[CH3:3][CH2:4][O:5][C:6]([CH:8](P(OCC)(OCC)=O)[F:9])=[O:7].N12CCCN=C1CCCCC2.[C:29]([N:36]1[CH2:41][CH2:40][CH:39]([CH:42]=O)[CH2:38][CH2:37]1)([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30]>C(#N)C>[F:9]/[C:8](=[CH:42]/[CH:39]1[CH2:40][CH2:41][N:36]([C:29]([O:31][C:32]([CH3:33])([CH3:35])[CH3:34])=[O:30])[CH2:37][CH2:38]1)/[C:6]([O:5][CH2:4][CH3:3])=[O:7]

Participants

6

Reactant 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 433294Lithium Chloride2×HCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateHCID 2734865Triethyl 2-fluoro-2-phosphonoacetate

Product 1

HCID 66561288(E)-ethyl 2-fluoro-3-(N-Boc-piperdin-4-yl)propenoate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

Compound 9 was prepared using the methods described in Scheme AE. Intermediate AE1 was prepared as follows. Lithium chloride (0.39 g) was added to a solution cooled to 0° C. of triethyl-2-fluoro-2-phophonoacetate (1.84 mL) and 1,8-diazabicyclo[5.4.0]undec-7-ene (1.15 mL) in acetonitrile (6 mL). The mixture was stirred until the lithium chloride was dissolved to form a homogeneous solution. N-Boc-piperidine-4-carboxaldehyde (1.61 g) in acetonitrile (2.0 mL) was added to the mixture and stirred for 24 h at room temperature. The reaction was quenched with saturated ammonium chloride (20 mL), diluted with ethyl acetate (150 mL), and washed with saturated sodium chloride (50 mL). The organic layer was dried (magnesium sulfate) and evaporated to yield 2.27 g of (E)-ethyl 2-fluoro-3-(N-Boc-piperdin-4-yl)propenoate (AE1). AE1 was carried forward as shown in Scheme AA to afford 9. Compound 9 was isolated as white flakes: mp 147-150° C.; MS m/e 515 (MH+). Anal. calcd. for C25H31FN6O5•2.3 HCl•1.6 H2O (627.25): C, 47.88; H, 5.87; N, 13.40; Cl, 13.00. Found: C, 48.26; H, 6.02; N, 12.90; Cl, 12.74.

Workup

  1. customIntermediate AE1 was prepared
  2. dissolutionwas dissolved
  3. customto form a homogeneous solution
  4. customThe reaction was quenched with saturated ammonium chloride (20 mL)
  5. additiondiluted with ethyl acetate (150 mL)
  6. washwashed with saturated sodium chloride (50 mL)
  7. dry with materialThe organic layer was dried (magnesium sulfate)
  8. customevaporated

Sources & evidence

ORD record
ord-4807315f10144c929101dbce57a0a0dd
Source dataset
uspto-grants-2001_10
Patent number
US06303625B1

Reaction notes

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