Diisopropylethylamine → tert-butyl N-[(2R,3R)-3-{(2S)-1[(9H-fluoren-9-ylmethoxy)carbonyl]pyrrolidin-2-yl}-3-methoxy-2-methylpropanoyl]-L-phenylalaninate

HRID 74775Notes

Reaction equation

HRID 74775 reaction equation
Cl.[NH2:2][C@H:3]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[CH:18]1[C:30]2[CH:29]([CH2:31][O:32][C:33]([N:35]3[CH2:39][CH2:38][CH2:37][C@H:36]3[C@H:40]([O:46][CH3:47])[C@@H:41]([CH3:45])[C:42](O)=[O:43])=[O:34])[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:22]=2[CH:21]=[CH:20][CH:19]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>ClCCl.CN(C=O)C.C(OCC)(=O)C>[CH:27]1[C:28]2[CH:29]([CH2:31][O:32][C:33]([N:35]3[CH2:39][CH2:38][CH2:37][C@H:36]3[C@H:40]([O:46][CH3:47])[C@@H:41]([CH3:45])[C:42]([NH:2][C@H:3]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:4][C:5]3[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=3)=[O:43])=[O:34])[C:30]3[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:23]=2[CH:24]=[CH:25][CH:26]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11459563L-Phenylalanine, 1,1-dimethylethyl ester, hydrochloride (1:1)HCID 58078476HCID 58078476, compound

Product 1

HCID 86762712tert-butyl N-[(2R,3R)-3-{(2S)-1[(9H-fluoren-9-ylmethoxy)carbonyl]pyrrolidin-2-yl}-3-methoxy-2-methylpropanoyl]-L-phenylalaninateYield 79%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirring solution of tert-butyl L-phenylalaninate, hydrochloride salt (1.67 g, 6.5 mmol, 1.0 eq.) and #119 (5.9 g, 6.5 mmol, 1.0 eq.) in 50 mL of dichloromethane and 5 mL of DMF, HATU (2.9 g, 7.9 mmol, 1.2 eq.) was added followed by Hunig's base (5.6 mL, 32 mmol, 5.0 eq.). The reaction was allowed to stir at room temperature for 45 minutes. Reaction was reduced down, diluted with ethyl acetate, washed with 0.5 N HCl and brine before being concentrated down onto silica. Silica chromatography was then performed (Gradient: 0%-25% acetone in heptane) producing #120 (3.14 g, 79%) as a white yellow solid. LC-MS (Protocol Q): m/z 613.1 [M+H+] retention time=2.37 minutes.

Workup

  1. customReaction
  2. washwashed with 0.5 N HCl and brine
  3. concentrationbefore being concentrated down onto silica

Sources & evidence

ORD record
ord-4fc36a71e7de46f78f3daae25ee71b0e
Source dataset
uspto-grants-2014_09
Patent number
US08828401B2

Reaction notes

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