Isobutyl chloroformate → tert-butyl (3R)-3-(9H-fluoren-9-ylmethoxycarbonylamino)-4-hydroxy-butanoate
Reaction equation
[NH:1]([C:14]([O:16][CH2:17][CH:18]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24]2[C:19]1=[CH:20][CH:21]=[CH:22][CH:23]=2)=[O:15])[C@@H:2]([C:11](O)=[O:12])[CH2:3][C:4](=[O:10])[O:5][C:6]([CH3:9])([CH3:8])[CH3:7].C(N(CC)C(C)C)(C)C.ClC(OCC(C)C)=O.[BH4-].[Na+]>C(OCC)(=O)C.CO.O1CCCC1>[CH:20]1[C:19]2[CH:18]([CH2:17][O:16][C:14]([NH:1][C@@H:2]([CH2:11][OH:12])[CH2:3][C:4]([O:5][C:6]([CH3:7])([CH3:9])[CH3:8])=[O:10])=[O:15])[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:24]=2[CH:23]=[CH:22][CH:21]=1Participants
8
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- -40 °C
Procedure
Fmoc-D-Asp(OtBu)-OH (9.0 g) and N,N-diisopropylethylamine (4.6 mL) were added to tetrahydrofuran (100 mL) and cooled to −40° C. Isobutyl chloroformate (3.1 mL) was added, and the solution was gradually warmed to 0° C. over 30 minutes. The solution was cooled to −20° C., and to it was carefully added sodium borohydride (1.64 g, 43.6 mmol) and methanol (10 mL). The solution was gradually warmed to room temperature over two hours, diluted with ethyl acetate (200 mL), washed with water (100 mL) and brine (50 mL), dried with anhydrous magnesium sulfate, filtered, and concentrated to afford crude product of sufficient purity for subsequent use.
Workup
- temperaturethe solution was gradually warmed to 0° C. over 30 minutes
- temperatureThe solution was cooled to −20° C.
- temperatureThe solution was gradually warmed to room temperature over two hours
- washwashed with water (100 mL) and brine (50 mL)
- dry with materialdried with anhydrous magnesium sulfate
- filtrationfiltered
- concentrationconcentrated
- customto afford crude product of sufficient purity for subsequent use
Sources & evidence
- ORD record
- ord-920307bf63e54e78942effe8eb34205d
- Source dataset
- uspto-grants-2015_07
- Patent number
- US09072748B2
Reaction notes
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