Hexane → 4-((tert-Butyldimethylsilyl)oxy)-1-(2-chloro-5-trityl-5H-pyrrolo[3,2-d]pyrimidin-7-yl)cyclohexanol

HRID 920671Notes

Reaction equation

HRID 920671 reaction equation
Br[C:2]1[C:6]2[N:7]=[C:8]([Cl:11])[N:9]=[CH:10][C:5]=2[N:4]([C:12]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:3]=1.[Li]CCCC.CCCCCC.[Si:42]([O:49][CH:50]1[CH2:55][CH2:54][C:53](=[O:56])[CH2:52][CH2:51]1)([C:45]([CH3:48])([CH3:47])[CH3:46])([CH3:44])[CH3:43]>C1COCC1>[Si:42]([O:49][CH:50]1[CH2:55][CH2:54][C:53]([C:2]2[C:6]3[N:7]=[C:8]([Cl:11])[N:9]=[CH:10][C:5]=3[N:4]([C:12]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH:3]=2)([OH:56])[CH2:52][CH2:51]1)([C:45]([CH3:48])([CH3:47])[CH3:46])([CH3:44])[CH3:43]

Participants

6

Reactant 4

HCID 8058HexaneHCID 106094304-(tert-Butyldimethylsilyloxy)cyclohexanoneHCID 867311637-bromo-2-chloro-5-trityl-5H-pyrrolo[3,2-d]pyrimidineHCID 178418339Butyllithium

Product 1

HCID 867311624-((tert-Butyldimethylsilyl)oxy)-1-(2-chloro-5-trityl-5H-pyrrolo[3,2-d]pyrimidin-7-yl)cyclohexanolYield 76%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 7-bromo-2-chloro-5-trityl-5H-pyrrolo[3,2-d]pyrimidine (2.00 g, 3.2 mmol) in THF (20 mL) was added a 2.5 N solution of BuLi in hexane (2.82 mL, 7.04 mmol) at −78° C. Then 4-((tert-butyldimethylsilyl)oxy)cyclohexanone (1.2 mL) was added after 15 min. The reaction was stirred at −78° C. for 3 hour, quenched with brine and extracted with EtOAc (3×). The combined organic layer was dried (MgSO4), filtered and concentrated. The residue was purified by ISCO to provide the desired product (1.52 g, 76%). 1H NMR (400 MHz, CDCl3, two isomers) δ 7.64-7.56 (m, 1H), 7.44-7.41 (m, 1H), 7.35-7.31 (m, 9H), 7.16-7.10 (m, 6H), 3.73-3.68 (m, 1H), 2.55-2.51 (m, 1H), 2.42-2.30 (m, 1H), 2.28-2.19 (m, 1H), 2.07-1.94 (m, 2H), 1.91-1.82 (m, 2H), 1.76-1.62 (m, 2H), 0.82 (s, 9H), 0.01 (s, 6H).

Workup

  1. customquenched with brine
  2. extractionextracted with EtOAc (3×)
  3. dry with materialThe combined organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by ISCO

Sources & evidence

ORD record
ord-5e7ab52073384eb49f9001b821a7540d
Source dataset
uspto-grants-2016_03
Patent number
US09273056B2

Reaction notes

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