Dimethyl Sulfoxide → (1R,3S,4S)-3-Formyl-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester

HRID 882793Notes

Reaction equation

HRID 882793 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[C:11]([O:15][C:16]([N:18]1[C@H:23]([CH2:24][OH:25])[C@@H:22]2[CH2:26][C@H:19]1[CH2:20][CH2:21]2)=[O:17])([CH3:14])([CH3:13])[CH3:12].CCN(C(C)C)C(C)C>C(Cl)Cl>[C:11]([O:15][C:16]([N:18]1[C@H:23]([CH:24]=[O:25])[C@@H:22]2[CH2:26][C@H:19]1[CH2:20][CH2:21]2)=[O:17])([CH3:14])([CH3:12])[CH3:13]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 66866104tert-butyl (1R,3S,4S)-3-(hydroxymethyl)-2-azabicyclo[2.2.1]heptane-2-carboxylate

Product 1

HCID 18396214(1R,3S,4S)-3-Formyl-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a cold (−60° C.) solution of oxalyl chloride (60.8 mmol) in dry DCM (130 mL) is added dropwise DMSO (111 mmol) within 5 min. After 15 min a solution of (1R,3S,4S)-3-hydroxymethyl-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (50.7 mmol) in dry DCM (40 mL) is added dropwise within 15 min. Stirring is continued for 45 min at −55° C., then DIPEA (253 mmol; dried over 3 A molecular sieve) is added during 5 min. The reaction mixture is allowed to reach rt and diluted with water (250 mL). The layers are separated and the organic layer is washed twice with aq. citric acid (5%, 200 mL each) and twice with brine. The combined organic layers are dried over MgSO4 and concentrated in vacuo to give the desired product which is used without further purification. 1H-NMR (CDCl3, 2 rotamers): δ=1.31-1.37 (m, 1H); 1.44 & 1.50 (2 s, 9H); 1.58-1.84 (m, 5H); 2.78 & 2.81 (2 bs, 1H); 3.60 & 3.74 (2 bs, 1H); 4.26 & 4.41 (2 bs, 1H); 9.55 & 9.60 (2 bs, 1H).

Workup

  1. customdried over 3 A molecular sieve)
  2. additionis added during 5 min
  3. customto reach rt
  4. additiondiluted with water (250 mL)
  5. customThe layers are separated
  6. washthe organic layer is washed twice with aq. citric acid (5%, 200 mL each) and twice with brine
  7. dry with materialThe combined organic layers are dried over MgSO4
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bbd6503854b44a5fa64ecba10592f446
Source dataset
uspto-grants-2012_08
Patent number
US08236801B2

Reaction notes

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