Acetic Acid → 2-acetamido-N-tert-butyl-2-((R)-1-(4-fluorobenzyl)pyrrolidin-3-yl)hex-5-enamide

HRID 579574Notes

Reaction equation

HRID 579574 reaction equation
[C:1]([NH:4][C:5]([C@@H:17]1[CH2:21][CH2:20][NH:19][CH2:18]1)([CH2:13][CH2:14][CH:15]=[CH2:16])[C:6]([NH:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])(=[O:3])[CH3:2].[F:22][C:23]1[CH:30]=[CH:29][C:26]([CH:27]=O)=[CH:25][CH:24]=1.C(O)(=O)C.C(Cl)Cl.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>>[C:1]([NH:4][C:5]([C@@H:17]1[CH2:21][CH2:20][N:19]([CH2:27][C:26]2[CH:29]=[CH:30][C:23]([F:22])=[CH:24][CH:25]=2)[CH2:18]1)([CH2:13][CH2:14][CH:15]=[CH2:16])[C:6]([NH:8][C:9]([CH3:11])([CH3:12])[CH3:10])=[O:7])(=[O:3])[CH3:2]

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 6344DichloromethaneHCID 680234-FluorobenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 668332862-acetamido-N-tert-butyl-2-[(3R)-pyrrolidin-3-yl]hex-5-enamide

Product 1

HCID 668329762-acetamido-N-tert-butyl-2-((R)-1-(4-fluorobenzyl)pyrrolidin-3-yl)hex-5-enamideYield 89.9%

Procedure

A solution of 2-acetamido-N-tert-butyl-2-[(3R)-pyrrolidin-3-yl]hex-5-enamide (315 mg, 1.07 mmol), 4-fluorobenzaldehyde (140 uL, 1.3 mmol) and acetic acid (60 uL, 1 mmol) in methylene chloride (10 mL, 200 mmol) was stirred for 10 minutes prior to the addition of sodium triacetoxyborohydride (377 mg, 1.78 mmol) in a single portion. After stirring at room temperature overnight, the reaction was quenched with 1 N NaOH (10 mL). The organic layer thus obtained was separated and the aqueous layer further extracted with DCM (3×10 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated to give 2-acetamido-N-tert-butyl-2-((R)-1-(4-fluorobenzyl)pyrrolidin-3-yl)hex-5-enamide (0.387 g, 89.9%) as an oil. The oil was used in the next step without purification. ESI MS found for C23H34FN3O2 m/z 404.3 (M+H)+.

Workup

  1. customthe reaction was quenched with 1 N NaOH (10 mL)
  2. customThe organic layer thus obtained
  3. customwas separated
  4. extractionthe aqueous layer further extracted with DCM (3×10 mL)
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-9050e8afb2e7479187096d820b29c7e6
Source dataset
uspto-grants-2015_05
Patent number
US09040703B2

Reaction notes

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