Dimethylformamide → (S)-ethyl 2-(1-(1-chloro-3-methylnaphthalen-2-yl)-2-(trityloxy)ethoxy)-2-methylpropanoate

HRID 926199Notes

Reaction equation

HRID 926199 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]([CH3:12])[C:3]=1[C@H:13]([OH:35])[CH2:14][O:15][C:16]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[H-].[Na+].[CH2:38]([O:40][C:41](=[O:47])[CH:42](Br)[CH2:43]CC)[CH3:39].[NH4+].[Cl-].[CH3:50]N(C=O)C>O>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]([CH3:12])[C:3]=1[C@H:13]([O:35][C:42]([CH3:43])([CH3:50])[C:41]([O:40][CH2:38][CH3:39])=[O:47])[CH2:14][O:15][C:16]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 24758Sodium hydride4×HCID 25517Ammonium ChlorideHCID 79071Ethyl 2-bromovalerate4×HCID 89676565(S)-1-(1-chloro-3-methylnaphthalen-2-yl)-2-(trityloxy)ethanol

Product 1

HCID 89681793(S)-ethyl 2-(1-(1-chloro-3-methylnaphthalen-2-yl)-2-(trityloxy)ethoxy)-2-methylpropanoate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A slurry of (S)-1-(1-chloro-3-methylnaphthalen-2-yl)-2-(trityloxy)ethanol (10.8 grams, 22.5 mmol) and DMF (40 mL) was treated with NaH (60% w/w in mineral oil, 11.3 mmol) at 23° C. After 5 min, ethyl-(2-bromovalerate) (1.65 mL, 11.3 mmol) was added. After 30 min had passed, more NaH (60% w/w in mineral oil, 11.3 mmol) was added. After stirring for 5 min, additional ethyl-(2-bromovalerate) (1.65 mL, 11.3 mmol) was added. Again, after 30 min had passed, more NaH (60% w/w in mineral oil, 11.3 mmol) was added. After stirring for 5 min, additional ethyl-(2-bromovalerate) (1.65 mL, 11.3 mmol) was added. Once more, after 30 min had passed, more NaH (60% w/w in mineral oil, 11.3 mmol) was added. After stirring for 5 min, additional ethyl-(2-bromovalerate) (1.65 mL, 11.3 mmol) was added. The reaction was stirred for another hour. Saturated aq. NH4Cl (100 mL) was added, followed by H2O (100 mL). After stirring for 10 min, the reaction was extracted with EtOAc (200 mL). The organic extract was washed with 5% w/v aq. LiCl (3×100 mL). The final organic phase was dried over Na2SO4, filtered, and concentrated. The residue was treated with benzene and purified by flash column chromatography (silica gel, 0 to 20% ethyl acetate/hexanes) to give (S)-ethyl 2-(1-(1-chloro-3-methylnaphthalen-2-yl)-2-(trityloxy)ethoxy)-2-methylpropanoate. 1H NMR (400 MHz, CDCl3) δ 8.30 (d, J=8.6 Hz, 1H), 7.70 (d, J=8.2 Hz, 1H), 7.57-7.38 (m, 2H), 7.49 (s, 1H), 7.36-7.32 (m, 6H), 7.21-7.14 (m, 9H), 5.94 (dd, J=6.7, 6.7 Hz, 1H), 3.93-3.74 (m, 2H), 3.61 (dd, J=9.0, 7.0 Hz, 1H), 3.33 (dd, J=9.0, 5.3 Hz, 1H), 2.52 (s, 3H), 1.46 (s, 3H), 1.37 (s, 3H), 0.99 (dd, J=7.0, 7.0 Hz, 3H). Additionally, starting material ((S)-1-(1-chloro-3-methylnaphthalen-2-yl)-2-(trityloxy)ethanol) was recovered. Yield was not determined.

Workup

  1. waitAfter 30 min had passed
  2. waitAgain, after 30 min had passed
  3. stirringAfter stirring for 5 min
  4. waitOnce more, after 30 min had passed
  5. stirringAfter stirring for 5 min
  6. stirringThe reaction was stirred for another hour
  7. stirringAfter stirring for 10 min
  8. extractionthe reaction was extracted with EtOAc (200 mL)
  9. extractionThe organic extract
  10. washwas washed with 5% w/v aq. LiCl (3×100 mL)
  11. dry with materialThe final organic phase was dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. additionThe residue was treated with benzene
  15. custompurified by flash column chromatography (silica gel, 0 to 20% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-cf58a8bc7e4541beb55764e5959fd6c9
Source dataset
uspto-grants-2016_03
Patent number
US09284323B2

Reaction notes

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