Synthesis of Cholesterol

C27H46O
Principal investigator | Robert Robinson |
---|---|
Publication year | 1953 |
Synthesis type | Formal |
Number of steps | 68 (linear) |
References |
Part 1 of 1
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HCl
Dioxane , H2O
RT, 30 min, 71% (3 steps)

MeI,
NaOMe
MeOH
RT to Reflux, 2 h, 50% (53% BRSM)



HI
AcOH, H2O
Reflux, 30-35 min, 58% (70% BRSM)

PtO2,
H2
1 atm
EtOH
RT, 65%

KOAc,
Ac2O
AcOH
Reflux, 1 h, 62% (95% BRSM)

H2,
Pd/SrCO3
150 atm
Dioxane
190-205 °C, 3 h, 63%


KOH
EtOH, H2O
Reflux, 60 min, 62% (2 steps)


Pyr
120 °C, 2 h, 9%
"Also isolated was other diastereomers (68% yield). The enantiomers were resolved with (-)-brucine."

KOH
H2O
100 °C, 20 min
"No yield reported."


K2CO3,
MeI
Acetone
Reflux, 20 h

KOH
MeOH
RT, 10 min


Br2,
HBr
AcOH, H2O
RT, 41%
"See: Helv. Chim. Acta 1950, 56, 389."

Pyr
6 h, 62%
"See: Helv. Chim. Acta 1950, 56, 389."

Ac2O,
AcCl
Reflux, 3 h, 79%

- KNH2
- NH4Cl
Et2O, NH3
-33 °C, 2 h

LiAlH4
Et2O
RT, 2 h, 6% (2 steps)

Ph3CCl
Pyr
100 °C, 4 h
"No yield reported."


HCl
CHCl3
0 °C to RT, 30 min, 29%
"Second relay molecule."

BzCl
Pyr
RT
"No yield reported."

- Ph3CNa
- CO2
Et2O, PhH
RT

CH2N2
Et2O
RT, 30 min, 16% (2 steps)
"Also isolated was a regioisomer (36% yield)"


NaOH
H2O, MeOH
Reflux, 27 h, 19% (2 steps)

PtO2,
H2
AcOH
RT, 76-80%

CH2N2
Et2O, MeOH
RT, 100%

Ac2O
Pyr
RT, 24 h, 87%

POCl3
Pyr
0 °C to Reflux, 90 min

H2,
PtO2
AcOH
RT, 20 h

HCl
MeOH
RT to Reflux, ON

BzCl
Pyr
RT, 60 min, 10% (4 steps)
"Third relay molecule"

K2CO3
H2O, MeOH
100 °C, 24 h, 95%

Ac2O
Pyr
Reflux, 80%

(COCl)2
PhH

CH2N2
Et2O, Petroleum ether
-5 °C, ON


KOH
MeOH
Reflux, 16 h

Ac2O
AcOH
Reflux, 6 h

15 mmHg
250-260 °C, 15% (6 steps)
"Fourth relay molecule"

"No conditions reported."


Br2,
HBr
AcOH, H2O
RT, 68-71%
"See: J. Org. Chem. 1948, 13, 697."


CrCl2
Acetone, H2O
RT, 30 min, 50-60% (2 steps)
"Fifth relay molecule. See: J. Am. Chem. Soc. 1950, 72, 4077."

Ac2O,
AcCl
Reflux, 3 h, 79%

- KNH2
- NH4Cl
Et2O, NH3
-33 °C, 2 h

LiAlH4
Et2O
RT, 5 h, 2.8% (2 steps)

Ph3CCl
Pyr
100 °C, 6 h, 1.6%


HCl
CHCl3
0 °C to RT, 30 min, 54%
"Sixth relay molecule."

Ac2O
Pyr
RT, ON, 84%
"See: J. Org. Chem. 1939, 4, 506."

KCN
AcOH, EtOH
RT, 30 min, 82%
"See: Chem. Ber. 1938, 71, 1487."

POCl3
Pyr
RT, 10 min, 58%
"See: Chem. Ber. 1938, 71, 1487."


Ni (Raney),
NaOH,
H2
EtOH, H2O
RT, 86%
"See: Chem. Ber. 1939, 72, 182."

Ac2O
Pyr
RT, 93%
"See: J. Org. Chem. 1939, 4, 506."

H2,
PtO2
AcOH
RT, 22 h
"see: Helv. Chim. Acta 1946, 29, 468."




Ac2O
Reflux, 30 min

H2,
PtO2,
HClO4
AcOH
RT, 15 min, 4.8% (3 steps)

Remaining...
(6 steps)
"See: Org. Synth. 1937, 17, 43; Ber. 1935, 68, 2091; Helv. Chim. Acta 1938, 21, 866; J. Chem. Soc. 1950, 2325; J. Am. Chem. Soc., 1952, 74, 4223."
