Benzyl Alcohol → N-(tert-Butoxycarbonyl)-(2S,4R)-4-fluoroproline benzyl ester

HRID 1527376Notes

Reaction equation

HRID 1527376 reaction equation
[C:1]([N:8]1[CH2:15][C@H:14]([F:16])[CH2:13][C@H:9]1[C:10]([OH:12])=[O:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C1CCC(N=C=NC2CCCCC2)CC1.[CH2:32](O)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:4]([O:3][C:1]([N:8]1[CH2:15][C@H:14]([F:16])[CH2:13][C@H:9]1[C:10]([O:12][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:11])=[O:2])([CH3:7])([CH3:6])[CH3:5]

Participants

6

Reactant 3

HCID 244Benzyl AlcoholHCID 10868DicyclohexylcarbodiimideHCID 12043048(2S,4R)-1-[(tert-butoxy)carbonyl]-4-fluoropyrrolidine-2-carboxylic acid

Product 1

HCID 68554319N-(tert-Butoxycarbonyl)-(2S,4R)-4-fluoroproline benzyl ester

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a suspension of N-Boc-trans-4-fluoro-L-proline (4.5 g, 19.29 mmol) in CH2Cl2 (68 mL) were added DCC (4.78 g, 23.15 mmol), DMAP (0.236 g, 1.93 mmol) and benzyl alcohol (2 mL, 19.29 mmol). The resulting white suspension was stirred at RT for 48 h and filtered. The filtrate was concentrated to give a colorless oil which was purified by flash column chromatography on silica gel (c-hexane to c-hexane/EtOAc 4-1) to give the desired compound. TLC, Rf (c-hexane/EtOAc 3:1)=0.3; MS: 346.0 [M+Na]+; tR (HPLC conditions a): 3.85 min.

Workup

  1. filtrationfiltered
  2. concentrationThe filtrate was concentrated
  3. customto give a colorless oil which
  4. customwas purified by flash column chromatography on silica gel (c-hexane to c-hexane/EtOAc 4-1)

Sources & evidence

ORD record
ord-890d4d9ea2e646c681ccb6cd502039f6
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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