Closed KlementineJBS closed 1 month ago
Followed protocol as in #190
Amounts: KBS48 - 92.4 mg, 0.103 mmol thiol (2,2 -(Ethylenedioxy)diethanethiol) - 0.411 mmol, 67 uL potassium carbonate - 0.821 mmol, 117.5 mg
Left heating at 80 C from 9 am.
TLC indicated consumption of SM even though two products were evident.
Worked up with ethyl acetate this time.
Ended up reextracting the combined LiCl washes as well (2 x 20 mL EtOAc, then washed with LiCl 2 x 20 mL and Na2CO3 solution).
1st extract vial: 15.6334 mass: 121.6 mg - quite wet
2nd extract vial: 15.7816
Signs of both singly and doubly deprotected product.
Singly deprotected: 742.20- [M-H]- Doubly deprotected: 531.26+, 553.33+, 562.15- (unsure what adduct this is?)
Fractions | Vial tare (g) | Mass (mg) | Substance |
---|---|---|---|
11-14 | thiol byproduct | ||
17-20 | |||
21-39 | 15.7827 | 9.9 | singly deprotected |
40-52 | 15.7319 | 23.8 | mixture |
53-55 | 15.6509 | doubly deprotected - product |
Turns out that "double spot" in fractions 40-52 was largely a trick of the eye -- NMR indicates it is quite cleanly bis product. Suggests that second thiol is indeed more effective.
Will combine 56-59 with 40-52 after confirming by TLC and purify via prep HPLC or other methods.
Note that F8 injection was probably contaminated by KBS44.
F6: No sign of any expected peaks except product. 936+, 515- and 521- are unclear. F7: Same as above. Unidentified peaks include 615-, 791+. F8: Tiny amount of 531+ product present. Mostly overpowered by previous injection.
KBS prep fractions 09-08-24 F8 retry.pdf KBS prep fractions 09-08-24 F7.pdf KBS prep fractions 09-08-24 F6.pdf KBS prep fractions 09-08-24 F2.d.zip
Tried F8 again. Seems to contain largely 559+ i.e. product of KBS44. Could be due to some kind of contamination from other samples. However, separation seems good so maybe not a big problem??
There is some trace of 531+ product.
F14/15 contains 531, 928 (KBS53 product, KBS44 SM) F15/16 contains 531 (KBS53 product) and nothing else
prep HPLCchecks.d.zip prep HPLC F15 or 16.pdf prep HPLC F14 or 15.pdf
Link to HIRAC and master page #186
KBS44 Nosyl deprotection of linear amines.docx
Reaction scheme
Outcome