반응 #158101

반응 방정식

methyl iodine

ACN H2O

(R)-3-tert-butoxycarbonylamino-4-(3′-chloro-biphenyl-4-yl)-butyric acid ethyl ester

LiHMDS THF

→

(R)-3-tert-butoxycarbonylamino-4-(3′-chloro-biphenyl-4-yl)-2-methyl-butyric acid ethyl ester

용매

THF

반응 조건

후처리

1. 1
   온도the reaction is slowly warmed up to room temperature
2. 2
   workup.STIRRINGstirred over night
3. 3
   기타The reaction is quenched by sat. NH4Cl
4. 4
   추출is extracted with EtOAc
5. 5
   세척The combined organic layer is washed with brine
6. 6
   건조dried over anhydrous sodium sulfate
7. 7
   여과filtered
8. 8
   농축concentrated
9. 9
   기타to give the crude

실험 절차

To a solution of (R)-3-tert-butoxycarbonylamino-4-(3′-chloro-biphenyl-4-yl)-butyric acid ethyl ester (300 mg, 0.718 mmol) in THF (10 ml) at −78° C. is added LiHMDS/THF (1M) (1.579 ml, 1.579 mmol). The reaction mixture is stirred at −78° C. for 50 min and then to this mixture is added methyl iodine (0.054 ml, 0.861 mmol) and the reaction is slowly warmed up to room temperature and stirred over night. The reaction is quenched by sat. NH4Cl and is extracted with EtOAc. The combined organic layer is washed with brine and dried over anhydrous sodium sulfate, filtered and concentrated to give the crude. Reverse phase HPLC [20 to 90% ACN—H2O (0.1% TFA) over 10 min by Sunfire C18] give (R)-3-tert-butoxycarbonylamino-4-(3′-chloro-biphenyl-4-yl)-2-methyl-butyric acid ethyl ester. LCMS (condition B): 432 (M+1); retention time=1.55 min. To a solution of (R)-3-tert-butoxycarbonylamino-4-(3′-chloro-biphenyl-4-yl)-2-methyl-butyric acid ethyl ester (240 mg, 0.556 mmol) in DCM (2 ml) at room temperature was added TFA (1.070 ml, 13.89 mmol) and the mixture is stirred at room temperature. 1 hr the reaction is done so the mixture is concentrated to give (R)-3-amino-4-(3′-chloro-biphenyl-4-yl)-2-methyl-butyric acid ethyl ester trifluoroacetate. LCMS (condition B): 332 (M+1); retention time=1.00 min.

출처