Diisopropylethylamine → [(R)-1-(3-fluoro-azetidine-1-carbonyl)-butyl]-carbamic acid tert-butyl ester

HRID 245923Notes

Reaction equation

HRID 245923 reaction equation
[C:1]([NH:8][C@@H:9]([C:13]([OH:15])=O)[CH2:10][CH2:11][CH3:12])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Cl.[F:17][CH:18]1[CH2:21][NH:20][CH2:19]1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:4]([O:3][C:1](=[O:2])[NH:8][C@@H:9]([C:13]([N:20]1[CH2:21][CH:18]([F:17])[CH2:19]1)=[O:15])[CH2:10][CH2:11][CH3:12])([CH3:5])([CH3:6])[CH3:7]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 6995000(2R)-2-(((tert-butoxy)carbonyl)amino)pentanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 101250543-fluoroazetidine Hydrochloride

Product 1

HCID 71279341[(R)-1-(3-fluoro-azetidine-1-carbonyl)-butyl]-carbamic acid tert-butyl esterYield 110.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A round-bottomed flask was charged with Boc-D-norvaline (300 mg, 1.38 mmol) and 3-fluoroazetidine hydrochloride (216 mg, 1.93 mmol). DMF (6 ml) was added followed by N,N-diisopropylethylamine (0.65 ml, 3.72 mmol) and HATU (578 mg, 1.52 mmol). The yellow reaction mixture was stirred at room temperature for 48 h the quenched with water and extracted with diethyl ether (2×). The combined organic layers were washed twice with water and once with brine then dried over sodium sulfate, filtered and concentrated to give 417 mg of [(R)-1-(3-fluoro-azetidine-1-carbonyl)-butyl]-carbamic acid tert-butyl ester as a light yellow solid.

Workup

  1. customquenched with water
  2. extractionextracted with diethyl ether (2×)
  3. washThe combined organic layers were washed twice with water and once with brine
  4. dry with materialthen dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-ea59b331e47d426182d8ae6c6a724198
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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