1-Hydroxybenzotriazole → HCID 67317845, compound

HRID 1042883Notes

Reaction equation

HRID 1042883 reaction equation
Cl.[F:2][C@H:3]1[CH2:7][NH:6][C@@H:5]([C:8]([O:10][CH3:11])=[O:9])[CH2:4]1.N1(O)C2C=CC=CC=2N=N1.[CH:22]1[C:34]2[CH:33]([CH2:35][O:36][C:37]([CH2:39][C:40](O)=[O:41])=[O:38])[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[C:26]=2[CH:25]=[CH:24][CH:23]=1.C(N(C(C)C)C(C)C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C(Cl)Cl.CN(C=O)C>[CH:31]1[C:32]2[CH:33]([CH2:35][O:36][C:37]([CH2:39][C:40]([N:6]3[CH2:7][C@H:3]([F:2])[CH2:4][C@@H:5]3[C:8]([O:10][CH3:11])=[O:9])=[O:41])=[O:38])[C:34]3[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:27]=2[CH:28]=[CH:29][CH:30]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 67316150HCID 67316150, compoundHCID 67318316methyl (2r,4r)-4-fluoropyrrolidine-2-carboxylate hydrochloride

Product 1

HCID 67317845HCID 67317845, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A pyrex reaction tube was charged with (2S,4R), (2R,4R)-methyl 4-fluoropyrrolidine-2-carboxylate hydrochloride (350 mg, 1906 μmol), 1H-benzo[d][1,2,3]triazol-1-ol (309 mg, 2287 μmol), 2-(((9H-fluoren-9-yl)methoxy)carbonyl)acetic acid (567 mg, 1906 μmol), N-ethyl-N-isopropylpropan-2-amine (996 μl, 5719 μmol) and 7.6 mL DMF. The mixture was stirred for 5 min at RT, and benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (1012 mg, 2287 μmol) was added, and the mixture was stirred at RT overnight. The mixture was diluted with DCM and washed with water. The organic portion was dried with MgSO4, filtered, concentrated, and then was concentrated twice from toluene to remove DMF. The crude oil was purified by silica gel chromatography DCM to 5% MeOH/DCM to provide (2S,4R), (2R,4R)-methyl 1-(2-(((9H-fluoren-9-yl)methoxy)carbonyl)acetyl)-4-fluoropyrrolidine-2-carboxylate as a waxy solid. MS: [M+H]=427.

Workup

  1. stirringthe mixture was stirred at RT overnight
  2. washwashed with water
  3. dry with materialThe organic portion was dried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. concentrationwas concentrated twice from toluene
  7. customto remove DMF
  8. customThe crude oil was purified by silica gel chromatography DCM to 5% MeOH/DCM

Sources & evidence

ORD record
ord-cd0e1c88088440c3aa402f4c66fc3291
Source dataset
uspto-grants-2013_10
Patent number
US08557816B2

Reaction notes

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