Sodium Hydroxide → 1-[(R)-tetrahydro-2-furoyl]-4-Boc-piperazine

HRID 2250364

Reaction equation

HRID 2250364 reaction equation
[O:1]1[CH2:5][CH2:4][CH2:3][C@@H:2]1[C:6]([OH:8])=O.S(Cl)(Cl)=O.[C:13]([N:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1)([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14].[OH-].[Na+]>C1(C)C=CC=CC=1.O>[O:1]1[CH2:5][CH2:4][CH2:3][C@@H:2]1[C:6]([N:23]1[CH2:22][CH2:21][N:20]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:25][CH2:24]1)=[O:8]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 24386Thionyl ChlorideHCID 143452tert-Butyl piperazine-1-carboxylateHCID 2734707Tetrahydro-2-furoic acid, (+)-

Product 1

HCID 668793671-[(R)-tetrahydro-2-furoyl]-4-Boc-piperazineYield 80.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent2×

Conditions

Temperature
90 °C

Procedure

To a solution of (R)-tetrahydro-2-furoic acid (5 g, 43.06 mmol) in toluene (75 mL) was added thionyl chloride (7.68 g, 64.6 mmol). The mixture was stirred at 90° C. for 2 h, then slowly cooled to 0° C. To a separate flask was charged a solution of N-Boc piperazine (8.02 g, 43.06 mmol) in toluene (40 mL), and aqueous sodium hydroxide (10.3 g, 258 mmol) in water (80 mL). This biphasic solution was cooled in an ice bath, followed by the addition of the cold acid chloride prepared above. The mixture was stirred vigorously for 2 h. The organic phase was collected, and washed with 1M H3PO4, dried and evaporated, to provide the title intermediate (9.87 g).

Workup

  1. temperatureslowly cooled to 0° C
  2. temperatureThis biphasic solution was cooled in an ice bath
  3. customprepared above
  4. stirringThe mixture was stirred vigorously for 2 h
  5. customThe organic phase was collected
  6. washwashed with 1M H3PO4
  7. customdried
  8. customevaporated

Sources & evidence

ORD record
ord-664b1f9e08424b888fba3e7d57d00609
Source dataset
uspto-grants-2008_01
Patent number
US07317022B2

Linked notes

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