Water → Rac-2-(tert-butoxycarbonylamino-methyl)-3-(7-fluoro-2-methoxy-quinolin-8-yl)-propionic acid ethyl ester

HRID 1259832

Reaction equation

HRID 1259832 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH2:11]([O:13][C:14](=[O:25])[CH2:15][CH2:16][NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH3:12].Br[CH2:27][C:28]1[C:29]([F:40])=[CH:30][CH:31]=[C:32]2[C:37]=1[N:36]=[C:35]([O:38][CH3:39])[CH:34]=[CH:33]2.O>C1COCC1.CC(=O)OCC>[CH2:11]([O:13][C:14](=[O:25])[CH:15]([CH2:16][NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:27][C:28]1[C:29]([F:40])=[CH:30][CH:31]=[C:32]2[C:37]=1[N:36]=[C:35]([O:38][CH3:39])[CH:34]=[CH:33]2)[CH3:12]

Participants

7

Reactant 4

HCID 962WaterHCID 2733832Lithium HexamethyldisilazideHCID 15933116Ethyl 3-{[(tert-butoxy)carbonyl]amino}propanoateHCID 66737650HCID 66737650, compound

Product 1

HCID 67181701Rac-2-(tert-butoxycarbonylamino-methyl)-3-(7-fluoro-2-methoxy-quinolin-8-yl)-propionic acid ethyl esterYield 75%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of LiHMDS (1M, 20 mL), cooled to −78° C., was added dropwise a solution of 3-tert-butoxycarbonylamino-propionic acid ethyl ester (2.01 g, 9.26 mmol; prepared according to Tetrahedron Lett. (2003), 44(14), 2807) in THF (20 mL). The solution was stirred at the same temperature for 90 min. A solution of 8-bromomethyl-7-fluoro-2-methoxy-quinoline (2.5 g, 1 eq., prepared according to WO 2007/081597) in THF (10 mL) was quickly added and the reaction proceeded 2 h, keeping the internal temperature below −50° C. Water (100 mL) and EA (200 mL) were added. The two layers were separated and the aq. layer was extracted with EA. The combined org. layers were washed with brine, dried over Na2SO4, filtered and concentrated to dryness. The residue was purified by CC (Hept-EA 2-1) to afford the title intermediate as a pale yellow oil which solidified after standing at rt for one day (2.83 g, 75% yield). MS (ESI, m/z): 407.3 [M+H+].

Workup

  1. waitthe reaction proceeded 2 h
  2. customthe internal temperature below −50° C
  3. customThe two layers were separated
  4. extractionthe aq. layer was extracted with EA
  5. washlayers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customThe residue was purified by CC (Hept-EA 2-1)

Sources & evidence

ORD record
ord-5859d27fedf84df187a55bf7c8b9fad4
Source dataset
uspto-grants-2013_06
Patent number
US08466168B2

Linked notes

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