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Dimethyl methylphosphonate → (7-tert-Butoxycarbonylamino-2-oxo-heptyl)-phosphonic acid dimethyl ester

HRID 860092
Notes
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Reaction equation

HRID 860092 reaction equation
[CH3:1][P:2](=[O:7])([O:5][CH3:6])[O:3][CH3:4].C([Li])CCC.O=C1CCC(=O)N1[O:20][C:21](=O)[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29]>C1COCC1>[CH3:4][O:3][P:2]([CH2:1][C:21](=[O:20])[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][NH:27][C:28]([O:30][C:31]([CH3:33])([CH3:32])[CH3:34])=[O:29])(=[O:7])[O:5][CH3:6]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 12958Dimethyl methylphosphonateHCID 5074016Boc-6-Ahx-OSuHCID 178418339Butyllithium

Product 1

HCID 20622500(7-tert-Butoxycarbonylamino-2-oxo-heptyl)-phosphonic acid dimethyl esterYield 105.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of dimethyl methylphosphonate (9.308 g, 75.01 mmol) in THF (30 mL) was cooled to −78 ° C. and treated with n-butyllithium (29.5 mL of 2.5 M). The reaction mixture was stirred at −78 ° C. for 10 min, followed by addition of 6-tert-butoxycarbonylamino-hexanoic acid 2,5-dioxo-pyrrolidin-1-yl ester (24-1) (5.060 g, 15.41 mmol) in THF (30 mL). After 15 min the reaction was quenched with aqueous NH4Cl and allowed to warm to room temperature overnight. The water was extracted three times with ethyl acetate and the combined organics washed with brine and dried (Na2SO4). The solvent was removed in vacuo to afford the title compound 24-2 as a pale yellow oil (5.5 g).

Workup

  1. customAfter 15 min the reaction was quenched with aqueous NH4Cl
  2. temperatureto warm to room temperature overnight
  3. extractionThe water was extracted three times with ethyl acetate
  4. washthe combined organics washed with brine
  5. dry with materialdried (Na2SO4)
  6. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-632d255c771449be809672fa3420dff6
Source dataset
uspto-grants-2006_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07153862B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes