Phosphorus oxychloride → (R)-benzyl 2-(4-chloro-6,6-dimethyl-5,6,7,8-tetrahydroquinazolin-2-yl)pyrrolidine-1-carboxylate

HRID 241024Notes

Reaction equation

HRID 241024 reaction equation
O[C:2]1[C:11]2[CH2:10][C:9]([CH3:13])([CH3:12])[CH2:8][CH2:7][C:6]=2[N:5]=[C:4]([C@H:14]2[CH2:18][CH2:17][CH2:16][N:15]2[C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:20])[N:3]=1.P(Cl)(Cl)([Cl:31])=O>C(Cl)(Cl)Cl>[Cl:31][C:2]1[C:11]2[CH2:10][C:9]([CH3:13])([CH3:12])[CH2:8][CH2:7][C:6]=2[N:5]=[C:4]([C@H:14]2[CH2:18][CH2:17][CH2:16][N:15]2[C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:20])[N:3]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178423967HCID 178423967, compound

Product 1

HCID 86647819(R)-benzyl 2-(4-chloro-6,6-dimethyl-5,6,7,8-tetrahydroquinazolin-2-yl)pyrrolidine-1-carboxylateYield 74%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

A mixture phenylmethyl(2R)-2-(4-hydroxy-6,6-dimethyl-5,6,7,8-tetrahydroquinazolin-2-yl)pyrrolidine-1-carboxylate (150 mg, 0.39 mmol) and phosphorous oxychloride (1 mL) in chloroform (3 mL) was stirred at 80° C. for one hour. After cooling to room temperature the reaction mixture was concentrated and the residue was partitioned between saturated sodium bicarbonate (20 mL) and ethyl acetate (20 mL). The mixture was stirred for 15 minutes and pH was maintained above 7 by the addition of solid sodium bicarbonate. The organic layer was separated and washed with water (10 mL) and brine, dried over sodium sulfate, filtered and concentrated to give phenylmethyl(2R)-2-(4-chloro-6,6-dimethyl-5,6,7,8-tetrahydroquinazolin-2-yl)pyrrolidine-1-carboxylate (117 mg, 74%). MS (EI) for C22H26ClN3O2: 400 (MH+).

Workup

  1. concentrationwas concentrated
  2. customthe residue was partitioned between saturated sodium bicarbonate (20 mL) and ethyl acetate (20 mL)
  3. temperaturepH was maintained above 7 by the addition of solid sodium bicarbonate
  4. customThe organic layer was separated
  5. washwashed with water (10 mL) and brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-ebce2406f175466db36a4c36580b8f94
Source dataset
uspto-grants-2014_02
Patent number
US08648066B2

Reaction notes

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