1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → [(S)-1-(4-Fluoro-benzyl)-2-(4-hydroxy-piperidin-1-yl)-2-oxo-ethyl]-carbamic acid tert-butyl ester

HRID 1693360Notes

Reaction equation

HRID 1693360 reaction equation
[C:1]([NH:8][C@H:9]([C:18]([OH:20])=O)[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Cl.[OH:22][CH:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C>CN(C=O)C>[C:4]([O:3][C:1](=[O:2])[NH:8][C@@H:9]([CH2:10][C:11]1[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=1)[C:18]([N:26]1[CH2:27][CH2:28][CH:23]([OH:22])[CH2:24][CH2:25]1)=[O:20])([CH3:5])([CH3:6])[CH3:7]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 7020910N-(tert-Butoxycarbonyl)-4-fluoro-L-phenylalanineHCID 162124994-Hydroxypiperidinium chloride

Product 1

HCID 10808894[(S)-1-(4-Fluoro-benzyl)-2-(4-hydroxy-piperidin-1-yl)-2-oxo-ethyl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of Boc-3-(4-fluorophenyl)-(S)-alanine (10.0 g, 35.3 mmol), 4-hydroxypiperidine hydrochloride (5.1 g, 37.1 mmol) and HOBt (7.2 g, 52.9 mmol) in DMF (100 mL), was added DIPEA (12.3 mL, 70.6 mmol) and after 5 min, EDCI (7.4 g, 38.8 mmol) and the reaction stirred at rt for 16 h. The solvent was removed in vacuo and the residue partitioned between water (150 mL) and ethyl acetate (2×150 mL). The combined organic fractions were washed with sodium hydroxide solution (2M, 50 mL), hydrochloric acid (2N, 50 mL), dried (MgSO4) and concentrated in vacuo. The product was chromatographed on silica gel eluting with ethyl acetate to give the title compound as a white solid. m/z (ES+)=367 [M+H]+; RT=3.28 min.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue partitioned between water (150 mL) and ethyl acetate (2×150 mL)
  3. washThe combined organic fractions were washed with sodium hydroxide solution (2M, 50 mL), hydrochloric acid (2N, 50 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe product was chromatographed on silica gel eluting with ethyl acetate

Sources & evidence

ORD record
ord-b7ba52887f884f37b6e7f46899af4a46
Source dataset
uspto-grants-2012_04
Patent number
US08158622B2

Reaction notes

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