tert-Butyl 4-oxopiperidine-1-carboxylate → 4-(2-Chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethylene)-piperidine-1-carboxylic acid tert-butyl ester

HRID 2262102Notes

Reaction equation

HRID 2262102 reaction equation
COP([CH2:7][C:8]1[S:16][C:15]2[C:14]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[N:13][C:12]([Cl:23])=[N:11][C:10]=2[CH:9]=1)(=O)OC.C([N-]C(C)C)(C)C.[Li+].[C:32]([O:36][C:37]([N:39]1[CH2:44][CH2:43][C:42](=O)[CH2:41][CH2:40]1)=[O:38])([CH3:35])([CH3:34])[CH3:33]>C1COCC1.C1COCC1.CCCCCCC.C(C1C=CC=CC=1)C>[C:32]([O:36][C:37]([N:39]1[CH2:44][CH2:43][C:42](=[CH:7][C:8]2[S:16][C:15]3[C:14]([N:17]4[CH2:18][CH2:19][O:20][CH2:21][CH2:22]4)=[N:13][C:12]([Cl:23])=[N:11][C:10]=3[CH:9]=2)[CH2:41][CH2:40]1)=[O:38])([CH3:35])([CH3:33])[CH3:34]

Participants

6

Reactant 3

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 2724682Lithium diisopropylamideHCID 86618396(2-Chloro-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-ylmethyl)phosphonic acid dimethyl ester

Product 1

HCID 866183974-(2-Chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethylene)-piperidine-1-carboxylic acid tert-butyl esterYield 90.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 22742125Tetrahydrofuran heptane ethylbenzolSolvent

Procedure

To a suspension of (2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-phosphonic acid dimethyl ester (0.80 gm) in THF (10 mL) at −78° C. was added dropwise lithium diisopropylamide (1.17 mL of a 2.0 M solution in THF/heptane/ethylbenzene). The mixture was warmed to room temperature and a solution of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (0.48 g) in THF (10 mL) was added via cannula. The mixture was then stirred at room temperature for 2 h, quenched with brine (20 mL) and extracted into dichloromethane (2×20 mL). The combined organics were dried (MgSO4), reduced in vacuo and purified by column chromatography to give 4-(2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethylene)-piperidine-1-carboxylic acid tert-butyl ester as a yellow oil (0.862 g).

Workup

  1. customquenched with brine (20 mL)
  2. extractionextracted into dichloromethane (2×20 mL)
  3. dry with materialThe combined organics were dried (MgSO4)
  4. custompurified by column chromatography

Sources & evidence

ORD record
ord-b36bac1de47f48f5942e9255ec9d9f1c
Source dataset
uspto-grants-2010_12
Patent number
US07846929B2

Reaction notes

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