Ammonium Chloride → HCID 69914526, compound

HRID 854004Notes

Reaction equation

HRID 854004 reaction equation
CCN(S(F)(F)[F:7])CC.[CH3:10][O:11][C:12]([CH:14]1[CH2:19][C:18]([CH2:21][CH:22]=[CH2:23])(O)[CH2:17][CH2:16][N:15]1[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[O:13].[NH4+].[Cl-]>C(Cl)Cl>[CH3:10][O:11][C:12]([CH:14]1[CH2:19][C:18]([F:7])([CH2:21][CH2:22][CH3:23])[CH2:17][CH2:16][N:15]1[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[O:13]

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 123472(Diethylamino)sulfur trifluorideHCID 69221321HCID 69221321, compound

Product 1

HCID 69914526HCID 69914526, compoundYield 52.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of DAST (0.55 g, 3.4 mmol) in DCM (5 mL) at −78° C., 4-hydroxyproline 12b (P=Boc, m=1, R9=n-butyl) (520 mg, 1.7 mmol) in dry DCM (5 mL) was added slowly. The mixture was stirred at −78° C. for 1 h and then at −10° C. for an additional 1 h. DCM (50 mL) was added, followed by aq. NH4Cl (10%, 30 mL). The organic layer was separated, dried over sodium sulfate and evaporated to dryness. The residue obtained was purified by column chromatography using 5% EtOAc in hexanes to obtain 4-fluoro-4-butylproline methyl ester 12c (P=Boc, m=1, R9=n-butyl) (270 mg, 52%) as a colorless oil: 1H NMR (300 MHz, CDCl3) δ 4.41 (m, 2), 3.83 (m, 1), 3.71 (s, 3), 3.45 (dd, J=12.3, 32.7, 2), 2.48 (m, 1), 1.73 (m, 2), 1.40 (m, 12), 0.89 (m, 3); MS (ESPOS): 326 [M+Na]+.

Workup

  1. waitat −10° C. for an additional 1 h
  2. customThe organic layer was separated
  3. dry with materialdried over sodium sulfate
  4. customevaporated to dryness
  5. customThe residue obtained
  6. customwas purified by column chromatography

Sources & evidence

ORD record
ord-9f17e3351ceb4ded824956da192cb99f
Source dataset
uspto-grants-2007_08
Patent number
US07256177B2

Reaction notes

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