Sulfuric Acid → 1-Benzhydryl-3-isopropylaminoazetidine-3-carboxylic Acid Amide

HRID 1246793Notes

Reaction equation

HRID 1246793 reaction equation
[CH:1]([N:14]1[CH2:17][C:16]([NH:20][CH:21]([CH3:23])[CH3:22])([C:18]#[N:19])[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:24]S(O)(=O)=O>C(Cl)Cl>[CH:1]([N:14]1[CH2:17][C:16]([NH:20][CH:21]([CH3:23])[CH3:22])([C:18]([NH2:19])=[O:24])[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 1118Sulfuric AcidHCID 219057861-(Diphenylmethyl)-3-[(propan-2-yl)amino]azetidine-3-carbonitrile

Product 1

HCID 587216991-Benzhydryl-3-isopropylaminoazetidine-3-carboxylic Acid Amide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 1-benzhydryl-3-isopropylaminoazetidine-3-carbonitrile (I-(7A-106)a; 3.40 g, 11.1 mmol) in methylene chloride (25 ml) cooled in an ice bath was treated with H2SO4 (5.95 ml, 111 mmol), dropwise. After the reaction mixture was allowed to warm to room temperature and stir overnight, it was cooled in an ice bath and then carefully quenched with concentrated NH4OH to pH 11. The mixture was extracted with methylene chloride, the combined organic layers were dried (Na2SO4) and then concentrated, in vacuo, to afford a crude foam (3.3 g) that was then purified on a Biotage™ Flash 40M column using 0–2% methanol in methylene chloride as eluant to afford the title compound I-(7A-106)b (2.32 g, 64%) as a brown solid: +ESI MS (M+1) 324.4; 1H NMR (400 MHz, CD3OD) δ 7.40 (d, J=7.5 Hz, 4H), 7.24 (t, J=7.5 Hz, 4H), 7.15 (t, J=7.1 Hz, 2H), 4.46 (s, 1H), 3.53 (d, J=8.7 Hz, 2H), 3.06 (d, J=8.7 Hz, 2H), 2.90 (septuplet, J=6.4 Hz, 1H), 0.97 (d, J=6.6 Hz, 6H).

Workup

  1. temperatureit was cooled in an ice bath
  2. customcarefully quenched with concentrated NH4OH to pH 11
  3. extractionThe mixture was extracted with methylene chloride
  4. dry with materialthe combined organic layers were dried (Na2SO4)
  5. concentrationconcentrated, in vacuo
  6. customto afford a crude foam (3.3 g) that
  7. customwas then purified on a Biotage™ Flash 40M column

Sources & evidence

ORD record
ord-84fbbc4bc0ab4700b53ae18613874588
Source dataset
uspto-grants-2006_10
Patent number
US07129239B2

Reaction notes

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