Diisopropylethylamine → [(R)-1-(3-cyano-azetidine-1-carbonyl)-2,2-dimethyl-propyl]-carbamic acid tert-butyl ester

HRID 245879Notes

Reaction equation

HRID 245879 reaction equation
[C:1]([NH:8][C@@H:9]([C:14]([OH:16])=O)[C:10]([CH3:13])([CH3:12])[CH3:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Cl.[NH:18]1[CH2:21][CH:20]([C:22]#[N:23])[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:14]([N:18]1[CH2:21][CH:20]([C:22]#[N:23])[CH2:19]1)=[O:16])[C:10]([CH3:11])([CH3:12])[CH3:13])([CH3:5])([CH3:6])[CH3:7]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 7005057(2R)-2-{[(tert-butoxy)carbonyl]amino}-3,3-dimethylbutanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 45072465Azetidine-3-carbonitrile hydrochloride

Product 1

HCID 71279421[(R)-1-(3-cyano-azetidine-1-carbonyl)-2,2-dimethyl-propyl]-carbamic acid tert-butyl esterYield 119.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A round-bottomed flask was charged with Boc-D-tert-leucine (300 mg, 1.3 mmol) and azetidine-3-carbonitrile hydrochloride (231 mg, 1.95 mmol). DMF (6 ml) was added followed by N,N-diisopropylethylamine (0.68 ml, 3.9 mmol) and HATU (543 mg, 1.43 mmol). The light yellow solution was stirred at room temperature for 48 h then 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 afford 458 mg of [(R)-1-(3-cyano-azetidine-1-carbonyl)-2,2-dimethyl-propyl]-carbamic acid tert-butyl ester as a light yellow oil.

Workup

  1. customthen quenched 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-5a14c4fe870146f090c27e393277ed11
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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