4-Methylmorpholine → 1454913-95-1

HRID 870947Notes

Reaction equation

HRID 870947 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([CH2:13][CH:14]1[CH2:18][CH2:17][CH2:16][CH2:15]1)[C:10](O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.ClC(OCC(C)C)=O.[BH4-].[Na+]>C1COCC1.O>[CH:14]1([CH2:13][CH:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:2])[CH3:4])[CH2:10][OH:11])[CH2:15][CH2:16][CH2:17][CH2:18]1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 34350992-(((Tert-butoxy)carbonyl)amino)-3-cyclopentylpropanoic acidHCID 4311764Sodium borohydride

Product 1

HCID 687141681454913-95-1Yield 72.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-10 °C

Procedure

To a solution of 2-((tert-butoxycarbonyl)amino)-3-cyclopentylpropanoic acid (730 mg, 2.84 mmol) in THF (7.5 mL) cooled to −10° C. was added N-methylmorpholine (0.312 mL, 2.84 mmol) followed by isobutyl chloroformate (0.373 mL, 2.84 mmol). The reaction mixture was then stirred for 5 min. The solid obtained was removed by filtration and washed with THF (5 mL). The filtrate was cooled to −10° C. and treated with NaBH4 (161 mg, 4.26 mmol) in water (5 mL) dropwise. The reaction mixture was stirred at −10° C. for 10 min and allowed to warm to room temperature and stirred for another 30 min. The reaction mixture was then quenched with cold water (5 mL). The aqueous layer extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with brine (20 mL), dried over sodium sulfate and concentrated under reduced pressure to afford a residue which was purified by column chromatography (pet ether: ethyl acetate) to afford tert-butyl 1-cyclopentyl-3-hydroxypropan-2-ylcarbamate (500 mg, 2.05 mmol, 72% yield). 1H NMR (400 MHz, DMSO-d6) δ 6.38 (m, 1H), 4.51 (m, 1H), 3.85-3.65 (m, 1H), 3.42 (m, 1H), 3.25 (m, 1H), 3.8 (m, 1H), 2.75 (m, 1H), 1.85-1.65 (m, 4H), 1.6-1.25 (m, 12H), 1.15 (m, 2H).

Workup

  1. customThe solid obtained
  2. customwas removed by filtration
  3. washwashed with THF (5 mL)
  4. stirringThe reaction mixture was stirred at −10° C. for 10 min
  5. temperatureto warm to room temperature
  6. stirringstirred for another 30 min
  7. customThe reaction mixture was then quenched with cold water (5 mL)
  8. extractionThe aqueous layer extracted with ethyl acetate (3×20 mL)
  9. washThe combined organic layers were washed with brine (20 mL)
  10. dry with materialdried over sodium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customto afford a residue which
  13. customwas purified by column chromatography (pet ether: ethyl acetate)

Sources & evidence

ORD record
ord-b0a885df1ae847c5b3ed2a9d10568a97
Source dataset
uspto-grants-2015_03
Patent number
US08969564B2

Reaction notes

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