Acetic Acid → 4-(N-tert-Butoxycarbonyl-N-isopropylamino)-1-(4-methoxypyrid-3-ylmethyl)piperidine

HRID 1181512Notes

Reaction equation

HRID 1181512 reaction equation
[C:1]([O:5][C:6]([N:8]([CH:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1)[CH:9]([CH3:11])[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:18][O:19][C:20]1[CH:25]=[CH:24][N:23]=[CH:22][C:21]=1[C:26]([O-])=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>ClC(Cl)C>[C:1]([O:5][C:6]([N:8]([CH:12]1[CH2:13][CH2:14][N:15]([CH2:26][C:21]2[CH:22]=[N:23][CH:24]=[CH:25][C:20]=2[O:19][CH3:18])[CH2:16][CH2:17]1)[CH:9]([CH3:11])[CH3:10])=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 261190644-Methoxypyridine-3-carboxylateHCID 50986573tert-butyl N-(piperidin-4-yl)-N-(propan-2-yl)carbamate

Product 1

HCID 674296194-(N-tert-Butoxycarbonyl-N-isopropylamino)-1-(4-methoxypyrid-3-ylmethyl)piperidineYield 105.9%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent2×

Procedure

A solution of 4-(N-tert-butoxycarbonyl-N-isopropylamino)piperidine (118 g, 0.49 mol) in dichloroethane (600 mL) was stirred at room temperature for 1 hour, and then 4-methoxypyridine-3-carboxylate (63.5 g, 0.46 mol) was added. The resulting solution was stirred at room temperature for 2.5 hours and then cooled to 5° C. in an ice/water bath. Sodium triacetoxyborohydride (124 g, 0.58 mol) in dichloroethane (600 mL) was added and the reaction mixture was stirred at 5° C. for 15 minutes. The ice bath was then removed and reaction mixture was stirred for 4 hours at room temperature. Acetic acid (30 mL) was then added to the reaction mixture and the resulting mixture was stirred for 0.5 hours, and then concentrated to half its original volume. This solution was cooled in a dry ice/acetone bath and 10 N aqueous sodium hydroxide (350 mL) was added. This mixture was stirred for 0.5 hours and then the organic layer was separated and washed with 1 N aqueous sodium hydroxide (400 mL). The aqueous layer was then washed three times with dichloromethane (400 mL) and the combined organic layers were dried over sodium sulfate (40 g). The sodium sulfate was filtered off and washed with dichloromethane (100 mL) and the combined organic layers were concentrated in vacuo to give 177 g of the title intermediate as a yellow oil (>99% yield; 74% purity by GC).

Workup

  1. temperaturecooled to 5° C. in an ice/water bath
  2. stirringthe reaction mixture was stirred at 5° C. for 15 minutes
  3. customThe ice bath was then removed
  4. customreaction mixture
  5. stirringwas stirred for 4 hours at room temperature
  6. stirringthe resulting mixture was stirred for 0.5 hours
  7. concentrationconcentrated to half its original volume
  8. temperatureThis solution was cooled in a dry ice/acetone bath
  9. addition10 N aqueous sodium hydroxide (350 mL) was added
  10. stirringThis mixture was stirred for 0.5 hours
  11. customthe organic layer was separated
  12. washwashed with 1 N aqueous sodium hydroxide (400 mL)
  13. washThe aqueous layer was then washed three times with dichloromethane (400 mL)
  14. dry with materialthe combined organic layers were dried over sodium sulfate (40 g)
  15. filtrationThe sodium sulfate was filtered off
  16. washwashed with dichloromethane (100 mL)
  17. concentrationthe combined organic layers were concentrated in vacuo

Sources & evidence

ORD record
ord-5dcdeaa9c112422fb99d3b2932ed47bf
Source dataset
uspto-grants-2007_10
Patent number
US07285564B2

Reaction notes

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