Hydrochloric Acid → (S)-N-((R)-(4-isobutoxyphenyl)((R)-pyrrolidin-2-yl)methyl)-2-phenylpropanamide

HRID 1874651Notes

Reaction equation

HRID 1874651 reaction equation
[CH2:1]([O:5][C:6]1[CH:11]=[CH:10][C:9]([C@@H:12]([NH:25][C:26](=[O:35])[C@H:27]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH3:28])[C@H:13]2[CH2:17][CH2:16][CH2:15][N:14]2C(OC(C)(C)C)=O)=[CH:8][CH:7]=1)[CH:2]([CH3:4])[CH3:3].Cl>>[CH2:1]([O:5][C:6]1[CH:7]=[CH:8][C:9]([C@H:12]([C@H:13]2[CH2:17][CH2:16][CH2:15][NH:14]2)[NH:25][C:26](=[O:35])[C@H:27]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH3:28])=[CH:10][CH:11]=1)[CH:2]([CH3:4])[CH3:3]

Participants

3

Reactant 2

HCID 313Hydrochloric AcidHCID 86658403(R)-tert-Butyl 2-((R)-(4-isobutoxyphenyl)((S)-2-phenylpropanamido)methyl)pyrrolidine-1-carboxylate

Product 1

HCID 58466412(S)-N-((R)-(4-isobutoxyphenyl)((R)-pyrrolidin-2-yl)methyl)-2-phenylpropanamideYield 16.9%

Procedure

(R)-tert-Butyl 2-((R)-(4-isobutoxyphenyl)((S)-2-phenylpropanamido)methyl)pyrrolidine-1-carboxylate (34.1 mg, 0.071 mmol) in hydrogen chloride (2M in diethyl ether) (355 mL, 0.710 mmol) was stirred at room temperature for 6 h then the solution was concentrated in vacuo. The residue was purified by HPLC (20%→100% acetonitrile/water with 0.1% TFA) to afford after preparing the free base, (S)-N-((R)-(4-isobutoxyphenyl)((R)-pyrrolidin-2-yl)methyl)-2-phenylpropanamide (4.6 mg, 0.012 mmol, 16.69% yield over two steps). 1H NMR (400 MHz, CDCl3) δ 7.40 (br s, 1H), 7.26-7.35 (m, 5H), 6.98 (d, J=8.56 Hz, 2H), 6.74 (d, J=8.81 Hz, 2H), 4.93 (t, J=7.18 Hz, 1H), 3.77 (q, J=7.05 Hz, 1H), 3.64-3.67 (m, 1H), 3.62 (d, J=6.55 Hz, 2H), 2.97-3.06 (m, 2H), 2.87-2.96 (m, 1 H), 1.96-2.09 (m, 1H), 1.67-1.83 (m, 3H), 1.53-1.57 (m, 1H), 1.50 (d, J=7.05 Hz, 3H), 0.97 (d, J=6.80 Hz, 6H); LRMS (ESI) m/e 381.30 [(M+H)+, calcd for C24H33N2O2 381.25].

Workup

  1. concentrationthe solution was concentrated in vacuo
  2. customThe residue was purified by HPLC (20%→100% acetonitrile/water with 0.1% TFA)
  3. customto afford

Sources & evidence

ORD record
ord-ee2c69a2571b42a3a6bbe524da274ec4
Source dataset
uspto-grants-2012_11
Patent number
US08304577B2

Reaction notes

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