Hydrochloric Acid → HCID 20068653, compound

HRID 981992Notes

Reaction equation

HRID 981992 reaction equation
C[Si](C)(C)N[Si](C)(C)C.[Li].[F:11][C:12]1[CH:13]=[N:14][C:15]([N:18]2[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:20][CH2:19]2)=[N:16][CH:17]=1.[F:32][C:33]1[C:42]2[C:37](=CC=CC=2)[C:36]([C:43](Cl)=[O:44])=[CH:35][CH:34]=1.Cl>C1COCC1.C(Cl)Cl>[F:32][C:33]1[CH:42]=[CH:37][C:36]([C:43]([CH:26]([CH2:25][CH2:24][N:21]2[CH2:20][CH2:19][N:18]([C:15]3[N:16]=[CH:17][C:12]([F:11])=[CH:13][N:14]=3)[CH2:23][CH2:22]2)[C:27]([O:29][CH2:30][CH3:31])=[O:28])=[O:44])=[CH:35][CH:34]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14700023HCID 14700023, compoundHCID 15729889HCID 15729889, compoundHCID 57426343Lithium bis(trimethylsilyl)amide

Product 1

HCID 20068653HCID 20068653, compoundYield 53.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a cold (-78° C.) solution of lithium 1,1,1,3,3,3-hexamethyl disilazane in tetrahydrofuran (27.4 mL, 1N, 27.4 mmol) kept under Ar atm was added dropwise (10 min) a solution of ethyl 4-(4-(5-fluoro-2-pyrimidinyl)piperazin-1-yl)butanoate (3.7 g, 12.5 mmol) in dry THF (12 mL). The reaction mixture was stirred 0.25 h at -78° C. and then treated dropwise (10 min) with a solution of 4-fluoro-1-naphthoyl chloride (2.6 g, 12.5 mmol) in dry THF (10 mL). The reaction was stirred -78° C. for 0.5 h then the cooling bath was removed. When the temperature of reaction mixture reached 0° C., HCl solution (40 mL, 0.3N) was added slowly followed by CH2Cl2 (350 mL); the organic phase was separated and aqueous phase was extracted with CH2Cl2 (120 mL). The organic extracts were combined, washed with water (2×45 mL) and brine, dried (MgSO4) and concentrated under reduced pressure to a crude mixture which was purified on a silica gel pad (8.7×2.5 cm). Evaporation of appropriate fractions gave 2.8 g (48%) of the desired product compound which was recrystallized from EtOH to give an analytical sample; mp 95°-6° C.; 1H NMR (CDCl3, 200 MHz) δ: 1.08 (t, J=7.1 Hz, CH3, 3H), 2.1-2.7 (m, 8H), 3.5-3.8 (m, 4H), 3.9-4.3 (m, 2H), 4.5-4.7 (m, 1H), 7.1-7.25 (m, 1H), 7.5-7.8 (m, 2H), 8.17 (s), 8.0-8.02 (s and m, 4H), 8.6-8.7 (m, 1H); IR (KBr) ν: 1740 (C=O, 1682, 1630, 1611, 1600, 1578, 1554, 1510 cm-1 ; UV (CH3CN) λ: 224 (ε 43570), 242 (ε 37740), 304 (ε 9084);

Workup

  1. stirringThe reaction was stirred -78° C. for 0.5 h
  2. customthe cooling bath was removed
  3. customWhen the temperature of reaction mixture
  4. customreached 0° C.
  5. customthe organic phase was separated
  6. extractionaqueous phase was extracted with CH2Cl2 (120 mL)
  7. washwashed with water (2×45 mL) and brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated under reduced pressure to a crude mixture which
  10. customwas purified on a silica gel pad (8.7×2.5 cm)
  11. customEvaporation of appropriate fractions

Sources & evidence

ORD record
ord-50e6b2f5e32441008151c659c9a034fc
Source dataset
uspto-grants-1991_02
Patent number
US04994460

Reaction notes

Loading…