تفاعل #158101

معادلة التفاعل

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

المذيبات

THF

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةthe reaction is slowly warmed up to room temperature
2. 2
   workup.STIRRINGstirred over night
3. 3
   أخرىThe reaction is quenched by sat. NH4Cl
4. 4
   استخلاصis extracted with EtOAc
5. 5
   غسيلThe combined organic layer is washed with brine
6. 6
   تجفيفdried over anhydrous sodium sulfate
7. 7
   ترشيحfiltered
8. 8
   تركيزconcentrated
9. 9
   أخرىto give the crude

الإجراء التجريبي

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.

المصدر