Isopropylamine → HCID 20664732, compound

HRID 1470260Notes

Reaction equation

HRID 1470260 reaction equation
C(N)(C)C.C([Li])CCC.[Li+].CC([N-]C(C)C)C.[CH3:18][O:19][C:20]([CH:22]1[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]1)=[O:21].[CH2:35](Br)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.[Cl-].[NH4+]>C1COCC1.CN(P(N(C)C)(N(C)C)=O)C>[CH3:18][O:19][C:20]([C:22]1([CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH2:23][CH2:24][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:26][CH2:27]1)=[O:21]

Participants

9

Reactant 6

HCID 6363IsopropylamineHCID 7498Benzyl BromideHCID 25517Ammonium ChlorideHCID 3928701-N-Boc-4-Piperidinecarboxylic acid methyl esterHCID 2724682Lithium diisopropylamideHCID 178418339Butyllithium

Product 1

HCID 20664732HCID 20664732, compoundYield 63%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 12679HexamethylphosphoramideSolvent

Procedure

To a solution of isopropylamine (1.34 ml, 9.559 mmol) in THF (40 ml) at 0° C. was added n-butyllithium (3.65 ml of a 2.5M sol. In hexanes, 9.125 mmol). The resulting LDA solution was added via cannula to a solution of piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4 methyl ester (2.11 g, 8.690 mmol) in THF (40 ml) and HMPA (8 ml) at −78° C. and stirring continued for 1 hour. Benzyl bromide (1.19 ml, 9.994 mmol) in THF (5 ml) was then added and the solution warmed to room temperature over 2 hours. After stirring for 18 h, saturated aqueous ammonium chloride (200 ml) was added and the aqueous phase extracted with diethyl ether (2×100 ml). Organic phases were combined, dried over magnesium sulphate and concentrated to dryness. Purification by silica column chromatography (0.5% methanol in DCM) gave the ester as an oil (1.816 g, 63%). LC/MS: (LCT) Rt 7.67 [M+H]+333.

Workup

  1. stirringAfter stirring for 18 h
  2. extractionthe aqueous phase extracted with diethyl ether (2×100 ml)
  3. dry with materialdried over magnesium sulphate
  4. concentrationconcentrated to dryness
  5. customPurification by silica column chromatography (0.5% methanol in DCM)

Sources & evidence

ORD record
ord-939a716d9c87409a992720416184dbf9
Source dataset
uspto-grants-2015_04
Patent number
US09006430B2

Reaction notes

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