Acetic Acid → (S)-2-Hydroxymethyl-azetidine-1-carboxylic acid benzyl ester

HRID 2389514Notes

Reaction equation

HRID 2389514 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:14][CH2:13][C@H:12]1[C:15](O)=[O:16])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B.CC(O)=O.C([O-])(O)=O.[Na+]>C1COCC1.O>[CH2:1]([O:8][C:9]([N:11]1[CH2:14][CH2:13][C@H:12]1[CH2:15][OH:16])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 6331BoraneHCID 516892Sodium BicarbonateHCID 12088656(2S)-1-(Benzyloxycarbonyl)azetidine-2-carboxylic acid

Product 1

HCID 10900173(S)-2-Hydroxymethyl-azetidine-1-carboxylic acid benzyl esterYield 89.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of (S)-Azetidine-1,2-dicarboxylic acid 1-benzyl ester (Starting material I-34f, 94 mg, 0.4 mmol) in 0.3 ml dry THF cooled to 0° C. is added dropwise 450 μl of a 1 M solution of borane in THF. The resulting solution is allowed to stir for 1 h at 0° C. and warm up to rt overnight. AcOH (1 ml) and water (1 ml) are then added as well as some saturated NaHCO3 solution in water until pH=9 and no more gas evolution occurs. The resulting aqueous phase is extracted three times with AcOEt. The combined organic phase is washed once with some saturated NaHCO3 solution in water and once with water. The solvents are evaporated in vacuo and the crude oil dried under high vacuum overnight, yielding the title compound (79 mg) in 89% as a colourless oil: tR=0.84 min (LC-3), ESI-MS (pos.): m/z 222.08 [M+H]+; 1H-NMR (CDCl3): δ (ppm) 2.00 (m, 1H, CH2CH2N), 2.22 (m, 1H, CH2CH2N), 3.78-4.01 (m, 5H, CH2N and CH2OH), 4.52 (s, 2H, OCH2Ph), 7.35 (s, 5H, Harom.). Starting material I-35e of the following Table 63 is prepared using a procedure analogous to that described for Starting material I-34e, substituting Starting material I-35f for I-34f.

Workup

  1. temperaturewarm up to rt overnight
  2. extractionThe resulting aqueous phase is extracted three times with AcOEt
  3. washThe combined organic phase is washed once with some saturated NaHCO3 solution in water and once with water
  4. customThe solvents are evaporated in vacuo
  5. customthe crude oil dried under high vacuum overnight

Sources & evidence

ORD record
ord-775cc5e9883d4dcd80513430cf9925aa
Source dataset
uspto-grants-2012_09
Patent number
US08273740B2

Reaction notes

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