Diisopropylethylamine → Retinol phosphoramidite

HRID 2307526Notes

Reaction equation

HRID 2307526 reaction equation
[CH3:1][C:2]1[CH2:7][CH2:6][CH2:5][C:4]([CH3:9])([CH3:8])[C:3]=1/[CH:10]=[CH:11]/[C:12](/[CH3:21])=[CH:13]/[CH:14]=[CH:15]/[C:16](/[CH3:20])=[CH:17]/[CH2:18][OH:19].C(N(C(C)C)CC)(C)C.C(CC[O:35][P:36](Cl)([N:38](C(C)C)C(C)C)=[O:37])#N.P(N)([O-])[O-].C([O-])(O)=O.[Na+]>CCN(CC)CC.CO.C(Cl)Cl>[CH3:1][C:2]1[CH2:7][CH2:6][CH2:5][C:4]([CH3:8])([CH3:9])[C:3]=1/[CH:10]=[CH:11]/[C:12](/[CH3:21])=[CH:13]/[CH:14]=[CH:15]/[C:16](/[CH3:20])=[CH:17]/[CH2:18][OH:19].[P:36]([NH2:38])([O-:37])[O-:35]

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 445354RetinolHCID 516892Sodium BicarbonateHCID 10080320PhosphoramiditeHCID 159279102-Cyanoethyl-n,n-diisopropylchlorophosphoramidate

Product 1

HCID 131722191Retinol phosphoramidite

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

All-trans-retinol (1 g) was vacuum dried and dissolved in anhydrous CH2Cl2 (10 ml) in an argon atmosphere. Diisopropylethylamine (2.65 ml, 21.5 mmol) was syringed in and the reaction mixture was cooled in an ice-bath. 2-cyanoethyl-N, N-diisopropylchlorophosphoramidate (2.5 g, 2.45 ml, 10.5 mmol) was slowly added by syringe under argon atmosphere. The reaction mixture was stirred for 30 min. at which time TLC (CH2Cl2:CH3OH:Et3N, 90:10:0.1) indicated complete conversion of the alcohol to its phosphoramidite. The reaction mixture was added to 100 ml of saturated NaHCO3 followed by washing the reaction flask with (2×25 ml) CH2Cl2. The CH2Cl2 layer was separated and washed with 100 ml of saturated NaCl solution and dried over anhydrous MgSO4 and evaporated into a yellow foam. The amidite was used directly in the DNA synthesizer without further purification since decomposition of this amidite was noted upon silica column purification.

Workup

  1. customdried
  2. dissolutiondissolved in anhydrous CH2Cl2 (10 ml) in an argon atmosphere
  3. temperaturewas cooled in an ice-bath
  4. washby washing the reaction flask with (2×25 ml) CH2Cl2
  5. customThe CH2Cl2 layer was separated
  6. washwashed with 100 ml of saturated NaCl solution
  7. dry with materialdried over anhydrous MgSO4
  8. customevaporated into a yellow foam
  9. customThe amidite was used directly in the DNA synthesizer without further purification since decomposition of
  10. customthis amidite was noted upon silica column purification

Sources & evidence

ORD record
ord-f6a04af7c23246629392a2ba220a1f24
Source dataset
uspto-grants-2004_12
Patent number
US06831166B2

Reaction notes

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