4-Fluorophenol → HCID 44600363, compound

HRID 882756Notes

Reaction equation

HRID 882756 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([OH:13])[CH2:10][C@H:9]1[C:14]([N:16]1[CH2:22][CH2:21][CH2:20][N:19]([CH:23]2[CH2:26][CH2:25][CH2:24]2)[CH2:18][CH2:17]1)=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:27][C:28]1[CH:33]=[CH:32][C:31](O)=[CH:30][CH:29]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1.[OH-].[Na+]>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([O:13][C:31]2[CH:32]=[CH:33][C:28]([F:27])=[CH:29][CH:30]=2)[CH2:10][C@H:9]1[C:14]([N:16]1[CH2:22][CH2:21][CH2:20][N:19]([CH:23]2[CH2:24][CH2:25][CH2:26]2)[CH2:18][CH2:17]1)=[O:15])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 97324-FluorophenolHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 44600522HCID 44600522, compound

Product 1

HCID 44600363HCID 44600363, compoundYield 44.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent

Procedure

To a solution of (2S,4R)-2-(4-cyclobutyl-[1,4]diazepane-1-carbonyl)-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester (1.74 g, 4.73 mmol) in THF (24 mL) was added 4-fluorophenol (795 mg, 7.10 mmol), triphenylphosphine (1.86 g, 7.10 mmol), and DEAD (1.12 mL, 7.10 mmol). After 48 h, the mixture was diluted with 1 M NaOH and extracted with CH2Cl2 (3×). The combined organic layers were dried and concentrated. Purification by FCC provided the desired product (969 mg, 44%). MS (ESI): mass calcd. for C25H36FN3O4, 461.27; m/z found, 462.6 [M+H]+. 1H NMR (CDCl3): 6.98-6.89 (m, 2H), 6.79 (dd, J=8.5, 4.1 Hz, 2H), 4.81-4.74 (m, 1H), 4.71-4.51 (m, 1H), 4.03-3.90 (m, 1H), 3.79-3.59 (m, 2H), 3.59-3.41 (m, 3H), 2.88-2.73 (m, 1H), 2.68-2.29 (m, 5H), 2.18-2.06 (m, 1H), 2.04-1.94 (m, 2H), 1.93-1.70 (m, 4H), 1.69-1.53 (m, 2H), 1.46-1.40 (m, 9H).

Workup

  1. extractionextracted with CH2Cl2 (3×)
  2. customThe combined organic layers were dried
  3. concentrationconcentrated
  4. customPurification by FCC

Sources & evidence

ORD record
ord-abe6601a28314854b984e8c6ea9943c4
Source dataset
uspto-grants-2012_08
Patent number
US08236792B2

Reaction notes

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